Predominantly platelet-shaped, sparingly water-soluble calcium salts and/or composite materials thereof comprising them

ABSTRACT

The invention relates to sparingly water-soluble calcium salts and/or composite materials comprising them, characterized in that the calcium salts are present in the form of single crystals or in the form of particles comprising a multitude of said crystals and having a mean particle diameter in the region of below 1,000 nm, preferably below 300 nm, the calcium salt particles being predominantly platelet-like. The inventive calcium salts and/or composite materials comprising these calcium salts, owing to their composition and fine structure, are particularly suitable for promoting the restoration of bone and tooth material, especially enamel and dentine.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation under 35 U.S.C. Sections 365(c) and120 of International Application No. PCT/EP2006/010235, filed Oct. 24,2006. This application also claims priority under 35 U.S.C. Section 119of German Patent Application No. DE 10 2006 009 799.8, filed Mar. 1,2006.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

Not Applicable

INCORPORATION-BY-REFERENCE OF MATERIAL SUBMITTED ON A COMPACT DISC

Not Applicable

BACKGROUND OF THE INVENTION

(1) Field of the Invention

The invention concerns sparingly water-soluble calcium salts and/orcomposite materials thereof comprising them, in which the calcium saltsare in the form of individual crystallites or of particles comprising amultiplicity of said crystallites, having a mean particle diameter inthe range of less than 1,000 nm, preferably less than 300 nm, and inwhich the calcium salt particles are predominantly platelet-like. Thecalcium salts according to the invention and/or composite materialscomprising these calcium salts are particularly suitable for promotingrestoration of bone and tooth material, especially enamel and dentine,because of their composition and fine structure.

Phosphate salts of calcium have long been added to formulations of toothcleaning and dental care materials both as abrasive components and forpromoting remineralization of dental enamel. That is particularly thecase for hydroxyapatite and fluoroapatite as well as for amorphouscalcium phosphates and for brushite (dicalcium phosphate dihydrate).Calcium fluoride has been described often as a component of toothcleaning agents and as a component to harden dental enamel and toprevent tooth decay.

The availability of calcium compounds for the desired remineralizationdepends quite critically on the particle sizes of these components thatare sparingly soluble in water and dispersed in the dental carematerials. It has, therefore, been suggested that these sparinglysoluble calcium salts be used at extremely fine particle sizes.

The dental enamel and the supporting tissue of the bones are composedpredominantly of the material hydroxyapatite. In the process of itsbiological formation, hydroxyapatite is layered in an ordered manner inthe protein matrix of the bone or tooth, which consists primarily ofcollagen. Thus the development of the hard load-bearing mineralstructure is controlled by the “matrix proteins,” which are made up ofcollagen an other proteins that adhere to the collagen and so provide astructured mineralization process that is also known asbiomineralization.

Bone material is a combination of scleroproteins and platelet-likehydroxyapatite.

(2) Description of Related Art, Including Information Disclosed Under 37C.F.R. Sections 1.97 and 1.98

Substances called “bone replacements,” which promote the naturalremineralization process, play an important part in restoration of bonematerial. Such substances are also required for coating implants inorder to achieve integral bonds between the bone and the implant, thatcan transfer even tensile forces. Coatings with high bioactivity, whichproduce effective osteogenesis at the bond, are particularly importanthere. In the state of the art, as is described, for example, by B. G.Willmann in Mat.-Wiss. u. Werkstofftech. 30 (1999) 317, hydroxyapatiteis generally applied to implants. The disadvantages of this procedureare the often insufficient acceleration of the biomineralizationprocess, flaking off of the hydroxyapatite layers, and theirunsatisfactory chemical stability.

Bone replacement materials that can be applied in liquid form are neededfor certain applications. However, those applications cannot be achievedin a satisfactory manner with the usual bone replacement materials.Beyond the disadvantages for applications technology (inadequatedispersibility of the solid components), the bone replacement materialsavailable to date which can be applied in liquid form have at best abiocompatible, perhaps absorbable effect, because of the coarselycrystalline inorganic components and the lack of organic components thatare similar to the biological ones. However, what is desired is naturalbiomineralization and, thus, osteoinductive, osteoconductive orosteostimulating materials that directly promote bone growth.

Among the bone replacement materials, composites of hydroxyapatite andcollagen are of particular interest because they resemble thecomposition of the natural bone. A similar situation prevails forreconstruction of tooth material: dentine consists of about 30% protein(essentially collagen) and 70% mineral substances (essentiallyhydroxyapatite). Enamel, in contrast, is made up of about 95%hydroxyapatite and 5% proteins.

Composite materials of the type described are accessible synthetically,such as described by B., Flautre et al. in J. Mater. Sci.: Mater. InMedicine 7 (1996) 63. However, in those composites, the particle sizesof the calcium salts are greater than 1,000 nm. That is too large togive a satisfactory biological action as a remineralization agent.

On the other hand, R. Z. Wang et al., J. Mater. Sci. Lett. 14 (1995) 49,describe a process for preparing a composite material of hydroxyapatiteand collagen, in which hydroxyapatite is deposited on the collagenmatrix in an evenly distributed form with a particle size range of 2 to10 nm. The composite material is said to have better biological activitythan other hydroxyapatite-collagen composites known in the state of theart because of the fine dispersion of the hydroxyapatite. However, asdescribed in the following, the composite material described by R. Z.Wang et al. does not satisfactorily meet the need for compositematerials that simulate the composition and microstructure of naturalbone and tooth material and are suitable for remineralization of thesenatural materials in a completely satisfactory manner.

EP 1 139 995 A1 suggests stabilizing suspensions of calcium salts thatare sparingly soluble in water in finely divided form during theirprecipitation or shortly thereafter, by performing the precipitation inthe presence of an agglomeration inhibitor or by redispersing thedispersion in the presence of an agglomeration inhibitor, such as aprotective colloid or surfactant.

WO 01/01930 discloses composite materials made up sparingly solublenanoparticulate calcium salts and protein components which haveremineralizing action on enamel and dentine. Type A or B gelatins areused for the purpose.

The documents cited do not describe calcium salts or composite materialscomprising them which have a predominantly platelet-like structure,exhibit strong mineralizing effects, and so produce particularlyeffective improvement of dental health even at short exposure times.

A further disadvantage of the protein-containing composite materialsknown in the state of the art is that they are often expensive toproduce. In the production of the composite of hydroxyapatite andcollagen described by R. Z. Wang et al., it is necessary to handleinsoluble collagen and to distribute it in quite large volumes ofsolvent. That is technologically expensive. This process also raisesadditional problems with respect to disposal of the wastewaters arisingfrom the production.

BRIEF SUMMARY OF THE INVENTION

It has now been found that certain materials are suitable for overcomingthe above-mentioned disadvantages of the state of the art.

Surprisingly, it has been possible to prepare calcium salts or compositematerials comprising them which have the sparingly water-soluble calciumsalts in a predominantly platelet-like structure.

BRIEF DESCRIPTION OF THE DRAWING

FIG. 1: TEM photograph of the platelet-like composite material preparedaccording to Example 2.1. Magnification at the instrument: 100,000×.

DETAILED DESCRIPTION OF THE INVENTION

The invention concerns sparingly water-soluble calcium salts and/orcomposite materials thereof comprising them, in which the calcium saltsare in the form of individual crystallites or of particles comprising amultiplicity of said crystallites, having a mean particle diameter inthe range of less than 1,000 nm, preferably less than 300 nm, and inwhich the calcium salt particles are predominantly rod-like orplatelet-like, preferably predominantly platelet-like. The particles ofthe calcium salts, made up of individual crystallites according to theinvention, can be of platelet or rod shape, depending on the conditionsof the production process.

The term “predominantly platelet-like” means that at least 50%,preferably at least 70%, and especially preferably at least 80% of theparticles are in the form of platelets.

It is particularly preferable for the particles to be of essentiallyplatelet-like form.

It is advantageous for the calcium salts or composite materialscomprising them to be particularly similar to the predominantlyplatelet-like calcium particles in the structure of the bone substancein vivo, which is also made up of platelets. That has the particularadvantage that they exhibit particularly good remineralizing andneomineralizing ability because of the similarity to the shape of thebiological apatites (such as bone or dentine apatite), so that theprocess of biomineralization can occur even faster and better.

A further advantage of the invention is that the sparingly water-solublecalcium salts or composite materials comprising them show improvedbiocompatibility with the predominantly platelet-like structure of thecalcium salts.

“Particle diameter” means, here, the diameter of the particles(crystallites or particles) in the direction of their greatestlongitudinal extent. The “mean particle diameter” is understood to bethe value averaged over the total amount of the composite. According tothe invention, it is less than 1,000 nm, preferably less than 300 nm.

It is preferable for the mean particle diameter of the crystallites tobe in the range of 10 to 150 nm, and particularly preferable for thecrystallites to have a thickness in the range of 2 to 50 nm and a lengthin the range of 10 to 150 nm. Here, “thickness” is understood to be thesmallest diameter of the crystallites, while “length” is their greatestdiameter.

The particle diameters of the crystallites can be determined by currentmethods known to those skilled in the art, especially by the broadeningof the reflections observed in x-ray diffraction. The evaluation ispreferably done by a fitting procedure such as the Rietveld method.

In a particularly preferred embodiment, the crystallites preferably havea thickness of 2 to 15 nm and a length of 10 to 50 nm. A thickness of 3to 11 nm and a length of 15 to 25 nm are particularly preferred.

According to a further preferred embodiment of the invention, theinventive calcium salts and/or the composite materials comprising themhave a mean particle diameter in the range of less than 1,000 nm,preferably less than 300 nm.

The particle diameters of the particles can be determined by currentmethods known to those skilled in the art, especially by evaluatingimaging processes, especially by transmission electron microscopy.

According to one particular embodiment the sparingly water-solublecalcium salts and/or composite materials comprising them haveplatelet-like particles with a width in the range of 5 to 150 nm and alength in the range of 10 to 150 nm as well as a height (thickness) of 2to 50 nm.

Here the height (thickness) is understood to be the smallest diameter ofthe particle with respect to the three mutually perpendicular spatialdirections, and the length is the greatest diameter. The width of theparticle is accordingly the other diameter perpendicular to the length,which is equal to or less than the longitudinal dimension of theparticle, but greater than or at least equal to its height dimension.

The platelet-like particles are more or less irregularly shapedparticles, some of which are rather round particles and some are ratherangular particles with rounded edges.

This can be seen particularly in the images that can be produced bytransmission electron microscopy (see FIG. 1).

In such samples the platelet-like particles often appear to overlap.Overlapping particles are generally imaged with greater blackening atthe sites of overlapping than are non-overlapping particles. Thelengths, widths and heights stated are preferably determined (measured)on non-overlapping particles.

The height of a platelet-like particle can preferably be obtained bydetermining the dimensions of the particle having its largest areaperpendicular to the plane of the image. The particles lyingperpendicular to the image plane are distinguished by particularly highcontrast (high blackening) and so appear rather rod-like. Theseplatelet-like particles lying perpendicular to the image plane can beidentified as actually perpendicular to the image plane if the dimensionincreases (in at least one spatial direction) and the density(blackening) of the image decreases on tilting of the image plane.

A particularly suitable means for determining the height of a particleis to tilt the image plane of the sample repeatedly into differentpositions and to determine the dimensions of the particle in theposition characterized by the highest contrast/greatest density and theminimum extent of the particle. Then the shortest extent corresponds tothe height of the particle.

According to one preferred embodiment, the average length of theparticles is preferably 30 to 100 nm.

The width of this particle is then in the range of 10 to 100 nm.

According to a special embodiment, the particles of the inventivesparingly soluble calcium salt and/or composite materials comprisingthem have a length to width ratio between 1 and 4, preferably between 1and 3, especially preferably between 1 and 2, such as 1.2 (length 60 nm,width 50 nm) or 1.5 (length 80, width 40 nm).

The platelet-like shape of the particle is formed by the ratio of lengthto width. If the ratio of length to width is clearly greater than 4, theparticles are rather rod-like.

The advantage of the platelet-like particle having a ratio of preferably1 to 2 is that these particles have a length to width ratio particularlysimilar to that of the natural bone material, and so exhibitparticularly good and biologically compatible remineralization orneomineralization of the tooth material (dentine and enamel).

According to a further special embodiment, the particles have an area of0.1·10⁻¹⁵ m² to 90·10⁻¹⁵ m², preferably an area of 0.5·10⁻¹⁵ m² to50·10⁻¹⁵ m², especially preferably 1.0·10⁻¹⁵ m² to 30·10⁻¹⁵ m², andquite particularly preferably 1.5·10⁻¹⁵ m² to 15·10⁻¹⁵ m², such as2·10⁻¹⁵ m².

The area of the particle is the area of the plane determined by thelength and the width perpendicular to it, according to the currentgeometrical calculation methods.

The present invention is surprisingly successful in producing thecalcium salts or composite materials comprising them, according to theinvention, in the form of crystalline inorganic nanoparticles whichresult in particularly effective neomineralization of tooth material(dentine and enamel) as well as bone tissue.

The term “sparingly soluble calcium salt” means those salts that aresoluble at less than 0.1% by weight (1 g/L) in water at 20° C. Examplesof such suitable salts include, for instance, calcium hydroxyphosphate(Ca₅[OH(PO₄)₃]), hydroxyapatite, calcium fluorophosphate (Ca₅[F(PO₄)₃)or fluoroapatite, fluoride-dosed hydroxyapatite having the compositionCa₅(PO₄)₃(OH, F) and calcium fluoride (CaF₂) or fluorite or fluorspar,as well as other calcium phosphates such as di-, tri- or tetra-calciumphosphate (Ca₂P₂O₇), Ca₃(PO₄)₂, Ca₄P₂O₉, oxyapatite (Ca₁₀(PO₄)₆O) ornon-stoichiometric hydroxyapatite(Ca_(5−1/2(x+y))(PO₄)_(3−x)(HPO₄)_(x)(OH)_(1−y). Carbonate-containingcalcium phosphates (such asCa_(5−1/2(x+y+z))(PO₄)_(3−x−z)(HPO₄)_(x)(CO₃)_(z)(OH)_(1−y)), calciumhydrogen phosphates (such as CaH(PO₄).2H₂O) and octacalcium phosphate(such as Ca₈H₂(PO₄)₆.5H₂O) are likewise suitable.

The composite materials according to the invention may preferablycontain as the calcium salt one or even more salts in a mixture,selected from the group of phosphates, fluorides and fluorophosphates,which may optionally also contain hydroxyl and/or carbonate groups.Hydroxyapatite and fluoroapatite are particularly preferred.

According to another embodiment of the invention, the crystallitesand/or particles of the calcium salts, which are free or in thecomposite materials according to the invention may be enveloped in oneor more surface-modification agents.

For example, the production of composite materials is made easier bythat means in cases in which it is difficult to disperse the calciumsalts. The surface-modification agent is adsorbed at the surface of thecrystallite and/or particle and changes it so as to increase thedispersibility of the calcium salt while the agglomeration of thecrystallites and/or particles is reduced or essentially prevented.

Furthermore, a surface modification can influence the structure of thesparingly soluble calcium salts and particularly of the compositematerials, as well as the charging of the polymer components with thecalcium salt. In this way, it is possible when using the compositematerials in remineralization processes to influence the course and rateof the remineralization process.

Surface-modification agents are understood to be substances that adherephysically to the surface of the finely divided particles but do notreact chemically with them. The individual molecules of thesurface-modification agents adsorbed at the surface are essentially freeof intermolecular bonds with each other. Surface-modification agents inthis meaning include, in particular, dispersing agents. Dispersingagents are also known to those skilled in the art as emulsifiers,protective colloids, wetting agents, detergents, etc.

For example, emulsifiers of the nonionic surfactant type from at leastone of the following groups can be considered as surface-modificationagents:

-   -   addition products of 2 to 30 moles of ethylene and/or 0 to 5        moles of propylene oxide to linear fatty alcohols having 8 to 22        C atoms, to fatty acids having 12 to 22 C atoms, and to        alkylphenols having 8 to 15 C atoms in the alkyl group;    -   C_(12/18) fatty acid monoesters and diesters of addition        products of 1 to 30 moles of ethylene oxide to glycerol;    -   glycerol monoesters and diesters and sorbitan monoesters and        diesters of saturated and unsaturated fatty acids having 6 to 22        carbon atoms and their ethylene oxide addition products;    -   alkyl monoglycosides and oligoglycosides having 8 to 22 carbon        atoms in the alkyl group and their ethoxylated analogs;    -   addition products of 15 to 60 moles of ethylene oxide to castor        oil and/or hardened castor oil;    -   polyol esters, especially polyglycerol esters, such as        polyglycerol polyricinoleate, polyglycerol        poly-12-hydroxystearate or polyglycerol dimerate. Mixtures of        compounds from this class of substances are also suitable.    -   addition products of 2 to 15 moles of ethylene oxide to castor        oil and/or hardened castor oil;    -   partial esters based on linear, branched, unsaturated or        saturated C_(6/22) fatty acids, ricinoleic acid and        12-hydroxystearic acid and glycerol, polyglycerol,        pentaerythritol, dipentaerythritol, sugar alcohols (such as        sorbitol), alkyl glycosides (such as methyl glucoside, butyl        glucoside, lauryl glucoside) and polyglucosides (such as        cellulose);    -   mono-, di- and tri-alkyl phosphates and mono-, di- and/or        tri-PEG-alkyl phosphates and their salts;    -   wool alcohols;    -   polysiloxane-polyalkyl-polyether copolymers or equivalent        derivatives;    -   mixed esters of pentaerythritol, fatty acids, citric acid and        fatty alcohols according to German Patent 1165574 and/or mixed        esters of fatty acids having 6 to 22 carbon atoms, methylglucose        and polyols, preferably glycerol or polyglycerol, and    -   polyalkylene glycols.

The addition products of ethylene oxide and/or propylene oxide to fattyalcohols, fatty acids, alkylphenols, glycerol monoesters and diesters,and sorbitan monoesters and diesters of fatty acids or to castor oil areknown products that are commercially available. They are mixtures ofhomologs. Their average degree of alkoxylation corresponds to the ratioof the amounts of ethylene oxide and/or propylene oxide and substratewith which the addition reaction is carried out.

C_(8/18) alkyl monoglycosides and oligoglycosides, their production, andtheir use, are known in the state of the art. They are producedprincipally by reaction of glucose or oligosacharides with primaryalcohols having 8 to 18 C atoms. With respect to the glycoside groups,both monoglycosides in which a cyclic sugar group is bondedglycosidically to the fatty alcohol and oligomeric glycosides having adegree of oligomerization up to preferably about 8 are suitable. Thedegree of oligomerization here is a statistical mean determined by theusual homolog distribution for such industrial products.

Typical examples of anionic emulsifiers include soaps, alkylbenzenesulfonates, alkane sulfonates, olefin sulfonates, alkyl ethersulfonates, glycerol ether sulfonates, α-methyl ester sulfonates,sulfofatty acids, alkyl sulfates, alkyl ether sulfates such as fattyalcohol ether sulfates, glycerol ether sulfates, hydroxy-mixed ethersulfates, monoglyceride(ether) sulfates, fatty acid amide (ether)sulfates, monoalkyl and dialkyl sulfosuccinates, monoalkyl and dialkylsulfosuccinamates, sulfo-triglycerides, amide soaps, ether carboxylicacids and their salts, fatty acid isethionates, fatty acid sarcosinates,fatty acid taurides, N-acylamino acids such as acylglutamate andacylaspartate, alkyl oligoglucoside sulfates, protein fatty acidcondensates (especially plant products based on wheat) and alkyl (ether)phosphates. To the extent that the anionic surfactants containpolyglycol ether chains, they may have a conventional, but preferably anarrower-range homolog distribution.

Zwitterionic surfactants can also be used as emulsifiers. Zwitterionicsurfactants are those surface-active compounds which have in themolecule at least one quaternary ammonium group and at least onecarboxylate and one sulfonate group. Particularly suitable zwitterionicsurfactants are the betaines such as N-alkyl-N,N-dimethylammoniumglycinates, such as cocoalkyl dimethyl ammonium glycinate,N-acylaminopropyl-N,N-dimethylammonium glycinates such ascocoacyl-aminopropyl dimethylammonium glycinate, and2-alkyl-3-carboxymethyl-3-hydroxyethylimidazoline, each having 8 to 18 Catoms in the alkyl or acyl group, andcocoacylaminoethyl-hydroxyethyl-carboxymethylglycinate. The fatty acidamide derivative known by the CTFA name cocamidopropyl betaine isparticularly preferred. Ampholytic surfactants are also suitableemulsifiers. Ampholytic surfactants are understood to be thosesurface-active compounds which have in the molecule, aside from aC_(8/18) alkyl or acyl group, at least one free amino group and at leastone —COOH or —SO₃H group and which can form internal salts. Examples ofsuitable ampholytic surfactants include N-alkylglycines,N-alkylpropionic acids, N-alkylaminobutyric acids,N-alkyliminodipropionic acids,N-hydroxyethyl-N-alkylamidopropyl-glycines, N-alkyltaurines,N-alkylsarcosines, 2-alkylaminopropionic acids and alkylaminoaceticacids, each having 8 to 18 C atoms in the alkyl group. Particularlypreferred ampholytic surfactants include N-cocoalkylaminopropionate,cocoacylaminoethylaminopropionate and C_(12/18)-acyl sarcosine.Quaternary emulsifiers can also be considered along with the ampholyticones. Those of the ester-quat type, preferably methyl-quaternizeddi-fatty acid triethanolamine ester salts, are particularly preferred.

Examples of protective colloids suitable as surface-modification agentsinclude, for instance, natural water-soluble polymers such as gumarabic, starches, water-soluble derivatives of water-insoluble polymericnatural substances, such as cellulose ethers like methycellulose,hydroxyethylcellulose, carboxymethylcellulose or modifiedcarboxymethylcellulose, hydroxyethyl starches or hydroxypropyl guar, aswell as synthetic water-soluble polymers such as polyvinyl alcohol,polyvinylpyrrolidone, polyalkylene glycols, polyaspartic acid andpolyacrylates.

The surface-modification agents are generally used at a concentration of0.1 to 50% by weight, but preferably 1 to 20% by weight, based on thecalcium salt.

Nonionic surfactants, in a proportion of 1 to 20% by weight, based onthe weight of the calcium salt, are outstandingly suitable assurface-modification agents. The nonionic surfactants of the type of thealkyl-C₈-C₁₆-(oligo)-glucosides and the ethoxylates of hardened castoroil have proven to be particularly effective.

According to a particular embodiment the composite materials accordingto the invention comprise

-   -   Sparingly water-soluble calcium salts, the calcium salts        occurring in the form of individual crystallites or in the form        of particles comprising a multiplicity of the said crystallites,        with a mean particle diameter in the range of less than 1,000        nm, preferably less than 300 nm, and    -   a polymer component        wherein the particles in the composite material are rod-like        and/or platelet-like, preferably predominantly platelet-like.

Composite materials are understood to be compound materials comprisingthe components specified in a) and b) and are microscopicallyheterogeneous but macroscopically homogeneous-appearing aggregates, andin which the crystallites or particles of the calcium salt occurassociated with the structure of the polymer component. The proportionof polymer components in the composite materials is between 0.1 and 80%by weight, preferably between 10 and 60, and especially between 30 and50% by weight, based on the total weight of the composite material.

The composite materials according to the invention are thereforestructured composite materials in contrast to the composite ofhydroxyapatite and collagen described by R. Z. Wang et al., in whichthere are evenly distributed hydroxyapatite nanoparticles. A furthersignificant difference between the object of the present invention andthe state of the art consists of the size and morphology of theinorganic component. The hydroxyapatite particles described by R. Z.Wang et al. have a size of 2-10 nm. Hydroxyapatite particles in thissize range are considered to be in the region of amorphous or partiallyx-ray amorphous materials.

A further advantage of the composite materials is that they do not tendto aggregate strongly, so that they can be processed better inproduction. In particular, improved dispersibility of the composite canbe observed.

According to a special embodiment, the polymer component is selectedfrom a protein component, protein hydrolysates and derivatives ofprotein hydrolysates.

One preferred embodiment of the invention consists of using proteinhydrolysates as the polymer component.

In the sense of the invention, polyacids and polybases may be consideredas the protein hydrolysate. The protein hydrolysates can be biopolymersor synthetic polymers. Thus the compositions according to the inventioncontain, for example, one or more protein hydrolysates selected from

-   -   alginic acids,    -   pectins,    -   carrageenan,    -   polygalacturonic acids,    -   amino and amino acid derivatives of alginic acids, pectins,        carrageenan and polygalacturonic acids,    -   polyamino acids such as polyaspartic acids,    -   polyaspartamides,    -   nucleic acids, such as DNA and RNA,    -   lignin sulfonates,    -   carboxymethylcelluloses,    -   cyclodextrin, cellulose, or dextran derivatives containing amino        groups and/or carboxyl groups,    -   polyacrylic acids,    -   polymethacrylic acids,    -   polymaleates,    -   polyvinylsulfonic acids,    -   polyvinylphosphonic acids,    -   polyethyleneimines,    -   polyvinylamines,        and derivatives of the substances named above, especially amino        and/or carboxyl derivatives. In the sense of the present        invention it is preferable to use protein hydrolysates bearing        groups suitable for forming salts with divalent cations.        Polymers bearing carboxylate groups are particularly suitable.

Electrolytes that are particularly preferred in the sense of theinvention are polyaspartic acids, alginic acids, pectins,deoxyribonucleic acids, ribonucleic acids, polyacrylic acids andpolymethacrylic acids.

Polyaspartic acids having molecular weights in the range between about500 and 10,000 Dalton, especially 1,000 to 5,000 Dalton, are quiteparticularly preferred.

Another preferred embodiment of the invention consists of selectingpolysaccharides as polymer components. In particular, thesepolysaccharides are selected from polysaccharides containing glucuronicacid and/or iduronic acid. That is understood to include thosepolysaccharides made up of, among other groups, glucuronic acid,preferably D-glucuronic acid and/or iduronic acid, especially L-iduronicacid. There glucuronic acid or iduronic acid forms part of thecarbohydrate structure. Iduronic acid, which is an isomer of glucuronicacid, has the opposite configuration at the C5 carbon atom of the ring.It is preferably understood that among the polysaccharides containingglucuronic acid and/or iduronic acid, those containing glucuronic acidor iduronic acid in a molar ratio of 1:10 to 10:1, preferably 1:5 to5:1, especially preferably 1:3 to 2:1, based on the sum of the othermonosaccharide components of the polysaccharide, are preferred.Particularly good interaction with the calcium salt can be attained bythe polysaccharides containing glucuronic acid and/or iduronic acidbecause of the anionic carboxyl groups of the glucuronic acid and/oriduronic acid. That results in a particularly stable and simultaneouslywell-mineralizing composite material. Examples of suitablepolysaccharides include the glycosaminoglycans (also known asmucopolysaccharides) containing glucuronic acid and/or iduronic acid,microbially produced xanthan or welan, or gum arabic, which is obtainedfrom acacias.

One advantage of the composite materials according to the invention istheir particular stability in aqueous systems, even without addition ofdispersant aids such as multifunctional alcohols (such as glycerol orpolyethylene glycols).

According to a particularly preferred embodiment the polymer componentis selected from a protein component, preferably from proteins, proteinhydrolysates and their derivatives.

Essentially all proteins, independently of their origin or preparation,can be considered as proteins in the context of the present invention.Examples of proteins of animal origin include keratin, elastin,collagen, fibroin, albumin, casein, whey protein, and placental protein.Of those, collagen, keratin, casein, and whey protein are preferredaccording to the invention. Proteins of plant origin, such as wheat andwheat germ proteins, rice protein, soy protein, oat protein, peaprotein, potato protein, almond protein and yeast protein can likewisebe preferred according to the invention.

In the sense of the present invention, degradation products of proteinssuch as collagen, elastin, casein, keratin, almond, potato, wheat, riceand soy protein which are obtained by acidic, alkaline, and/or enzymatichydrolysis of the proteins themselves, or their degradation productssuch as gelatin, are understood to be protein hydrolysates. Allhydrolytic enzymes are suitable for the enzymatic degradation, forinstance, alkaline proteases. Other suitable enzymes and enzymatichydrolysis procedures are described, for instance, in K. Drauz and H.Waldmann, Enzyme Catalysis in Organic Synthesis, VCH-Verlag, Weinheim,1975. On degradation, the proteins are split into smaller subunits. Thedegradation can pass through the stages of polypeptides througholigopeptides to the individual amino acids. The less-degraded proteinsinclude particularly the gelatins that are preferred in the context ofthe present invention. They can have molecular weights in the range of15,000 to 250,000 Daltons. Gelatin is a polypeptide obtained primarilyby hydrolysis of collagen under acidic conditions (Gelatin type A) oralkaline conditions (Gelatin type B). The gel strength of the gelatin isproportional to its molecular weight. That is, a more stronglyhydrolyzed gelatin yields a less viscous solution. The gel strength ofthe gelatin is reported in Bloom numbers. In the enzymatic splitting ofgelatin, the size of the polymer is greatly reduced, resulting in verylow Bloom numbers.

The protein hydrolysates commonly used in cosmetics, having averagemolecular weights in the range of 600 to 4,000, especially preferably2,000 to 3,500, are also used preferably as protein hydrolysates in thecontext of the present invention. Surveys on production and use ofprotein hydrolysates are, for example, those by G. Schuster and A.Domsch in Seifen Öle Fette Wachse [Soaps, Oils, Fats, Waxes] 108 (1982)177 or Cosm. Toil. 99 (1984) 63, by H. W. Steisslinger in Parf. Kosm. 72(1991) 556, and F. Aurich et al. in Tens. Surf. Det. 29 (1992) 389.Protein hydrolysates from collagen, keratin, casein and plant proteinsare used preferably according to the invention, especially those basedon wheat gluten or rice protein. Their preparation is described in twoGerman patents, DE 19502167 C1 and DE 19502168 C1 (Henkel).

In the context of the present invention, protein hydrolyzate derivativesare understood to include chemically and/or chemoenzymatically modifiedprotein hydrolysates such as these compounds, known by their INCI names:sodium cocoyl hydrolyzed wheat protein laurdimonium hydroxypropylhydrolyzed wheat protein, potassium cocoyl hydrolyzed collagen,potassium undecylenoyl hydrolyzed collagen and laurdimoniumhydroxypropyl hydrolyzed collagen. Derivatives of protein hydrolysatesof collagen, keratin and casein and of plant protein hydrolysates suchas sodium cocoyl hydrolyzed wheat protein or laurdimonium hydroxypropylhydrolyzed wheat protein are used preferably according to the invention.

Other examples of protein hydrolysates and protein hydrolyzatederivatives that are within the scope of the present invention aredescribed in CTFA 1997 International Buyers Guide, John A. Wenninger etal. (Ed.), The Cosmetic, Toiletry, and Fragrance Association, WashingtonD.C. 1997, 686-688.

In each of the composite materials according to the invention, theprotein component can be made up of one or more substances selected fromthe group of proteins, protein hydrolysates and protein hydrolyzatederivatives.

All the structure-forming proteins, protein hydrolysates and proteinhydrolyzate derivatives are preferred as protein components. Thoseprotein components are understood to be those which formthree-dimensional spatial structures because of their chemicalconstitution. They are familiar to those skilled in the art from proteinchemistry under the concepts of secondary, tertiary, or even quaternarystructure.

According to a particularly preferred application, the protein componentof the composite material is selected from collagen, gelatins, casein,and their hydrolysates, preferably gelatins, especially preferablygelatin of Type A, B or AB, and particularly Gelatins of the acid bonetype.

According to a particularly preferred embodiment, gelatins of Type ABcan be used. They are also known by the names “acid bone” or “acidprocess ossein” gelatins, and are produced from ossein under stronglyacidic process conditions.

Ossein, the collagen-containing starting material for producing gelatinsof Type AB, “acid bone” or “acid process ossein,” is made as an extractof ground bone, especially beef bone, After optional defatting anddrying, it is held for one or more days (preferably at least a week ormore) in aqueous solution, preferably cold acid, preferably dilute acid(e.g., hydrochloric acid) to remove the inorganic components of thebone, especially hydroxyapatite and calcium carbonate. This produces aspongy demineralized bone material, ossein.

The collagen in the ossein is denatured and released by a digestionprocess in which the material is treated under strongly acidicconditions.

The gelatins are produced from the raw materials named by multipleextraction with aqueous solutions. The pH of the solution can preferablybe adjusted before the extraction process. Multiple extraction stepswith water or aqueous solutions at increasing solvent temperature areespecially preferable.

Composite materials that can be obtained from a sparingly water-solublecalcium salt with gelatins of Type AB (acid-bone) are particularlysuitable for use in the applications according to the invention.

Now it has been found, surprisingly, that the composite materialscontaining gelatins of Type AB, “acid bone,” exhibit particularly strongneomineralization. Composite materials that can be obtained from asparingly water-soluble calcium salt with gelatins of Type AB(acid-bone) are thus particularly suitable for use in bones and teeth(see Examples). The composite materials according to the invention aretherefore preferred, in comparison with the composites named, for use,especially for rapid sealing of dentinal tubules, for remineralizationof the tooth material, for use in teeth and bones to prevent and/ortreat damage due to external influences, especially physiological,chemical, physical and/or microbiological in nature, e.g., in case oferosion, primary lesions and initial caries, as well as for cariesprophylaxis, to improve resistance to mechanical stress and generally toimprove the cleaning properties of the teeth and dental health ingeneral.

The sparingly water-soluble calcium salts or composite materialscomprising them can be produced by precipitation reactions from aqueoussolutions of water-soluble calcium salts and aqueous solutions ofwater-soluble phosphate and/or fluoride salts. In the case of thecomposite materials according to the invention the precipitation iscarried out in the presence of polymer components.

The composite materials according to the invention are preferablyproduced by adding the polymer components in pure, dissolved orcolloidal form to the neutral or alkaline aqueous phosphate and/orfluoride salt solution or to the neutral or alkaline solution of thecalcium salt before the precipitation reaction. Alternatively, thepolymer components can be made up in pure, dissolved or colloidal formand then mixed, successively in arbitrary sequence, or simultaneously,with the neutral or alkaline calcium salt solution and with the neutralor alkaline phosphate and/or fluoride salt solution. “Neutral solutions”are to be understood as solutions having a pH between about 6.5 andabout 7.5.

In the production process according to the invention, the individualcomponents can fundamentally be combined in all possible sequences.Ammonia is used preferably as the alkalizing agent.

A further variant of the production process according to the inventionconsists of performing the precipitation from an acidic solution of awater-soluble calcium salt together with a stoichiometric quantity of awater-soluble phosphate and/or fluoride salt or from an acidic solutionof hydroxyapatite having a pH below 5, preferably at a pH below 3, byraising the pH with aqueous alkali or ammonia in the presence of thepolymer components.

A further variant of the process consists of mixing nanoparticulatecalcium salts in pure or dispersed form, or dispersions ofnanoparticulate calcium salts prepared by precipitation reactions fromaqueous solutions of water-soluble calcium salts and aqueous solutionsof water-soluble phosphate and/or fluoride salts with the polymercomponents, the latter preferably in dissolved or dispersed form. Anydesired sequence can be selected for the addition.

It is preferable to start with the solution or dispersion of the polymercomponents and to add a dispersion of the nanoparticulate calcium saltto it.

For all the production processes mentioned, the resulting dispersion ofthe composite material can be separated from solvents and the othercomponents of the reaction mixture as needed by processes known to thoseskilled in the art, such as filtration or centrifugation, and isolatedin the solvent-free form by subsequent drying, such as freeze-drying.

Water is the preferred solvent in all the production processes, butorganic solvents, such as monofunctional or polyfunctional alcohols with1 to 4 C atoms, or glycerol, can also be used in individual steps ofproduction.

The calcium salts or composite materials comprising them, and inparticular those composite materials having a protein component selectedfrom collagen, casein or gelatins, preferably gelatins of the AB type,with surface-modified crystallites and/or particles of the calcium salt,can be produced by precipitation reactions analogous to those describedabove, but in which the precipitation of the nanoparticulate calciumsalt or the composite materials is carried out in the presence of one ormore surface-modification agents.

It is preferable to produce the surface-modified nanoparticulate calciumsalt by an initial precipitation reaction between aqueous solutions ofcalcium salts and aqueous solutions of phosphate and/or fluoride saltsin the presence of the surface-modification agent. They can then befreed of byproducts in the reaction mixture, for instance, byevaporation under reduced pressure and subsequent dialysis. In addition,a dispersion of the surface-modified calcium salt having a desiredproportion of solids can be made by removal of the solvent. Then thecomposite material of surface-coated calcium slat and polymer componentsis made by adding the polymer components in pure, dissolved or colloidalform, with the sequence of the addition again noncritical, and, ifnecessary, a further reaction at elevated temperature, preferably in therange between 50 and 100° C. and for a duration of 1 to 100 minutes,forming the composite material from the surface-coated calcium salt andthe polymer components.

Precipitation of the calcium salt or of the composite material at a pHbetween 5 and 9, preferably between 6 and 8, especially preferably about7, is particularly suitable for producing a calcium salt or compositematerial according to the invention which contains predominantlyplatelet-like particles.

To develop the composite materials preferred according to the inventionit is preferable to make a solution of a calcium salt with the polymercomponent and to add to it, slowly, a phosphate solution, with the pHbetween 5 and 9, preferably between 6 and 8, and particularly preferablyabout 7. It is especially preferable to hold the pH constant duringaddition of the phosphate solution by adding appropriate quantities ofan aqueous base.

Other processes, such as those described in German Patent Application DE19858662.0, can be used to produce dispersions of surface-modifiedcalcium salts.

The calcium salts or composite materials containing them according tothe invention, and in particular those composite materials having aprotein component selected from collagen, casein or gelatins, especiallypreferably gelatins of types A, B or AB, and especially gelatin of theacid bone type, those of hydroxyapatite, fluoroapatite and calciumfluoride, are suitable as mineralizing components to productcompositions for cleaning teeth and/or dental care.

The effect of hardening the enamel and closure of lesions and dentinaltubules occurs particularly rapidly and completely because of thestructured form, particularly of the preferred composite and theparticle size of the calcium compounds contained therein.

Furthermore, calcium salts or composite materials comprising themaccording to the invention, and especially those composite materialshaving a protein component selected from collagen, casein or gelatins,especially preferably gelatins of Types A, B or AB, particularly gelatinof the acid bone type, can be used as neomineralizing or remineralizingcomponents in compositions for hardening the enamel.

Another use of the calcium salts or composite materials comprising them,and especially those composite materials having a protein componentselected from collagen, casein or gelatins, especially preferablygelatins of Types A, B or AB, particularly gelatin of the acid bone typeis as components for inducing or promoting biomineralization fortreatment of tooth or bone defects.

The calcium salts or composite materials comprising them according tothe invention, and especially those composite materials having a proteincomponent selected from collagen, casein or gelatins, especiallypreferably gelatins of Types A, B or AB, particularly gelatin of theacid bone type, or compositions containing them, can also be used tocoat implants.

It is also preferred to use the calcium salts or composite materialscomprising them according to the invention, and especially thosecomposite materials having a protein component selected from collagen,casein or gelatins, especially preferably gelatins of Types A, B or AB,particularly gelatin of the acid bone type, or compositions containingat least those, to smooth the surfaces of teeth and/or bones.

The calcium salts or composite materials comprising them according tothe invention, and especially those composite materials having a proteincomponent selected from collagen, casein or gelatins, especiallypreferably gelatins of Types A, B or AB, particularly gelatin of theacid bone type, especially those of hydroxyapatite and fluoroapatite,can induce or promote biomineralization in bone tissue. Thus they arefurther suitable as biomineralizing components to make compositions forrestoring or new formation of bone material, e.g., compositions fortreating bone defects and bone fractures and to promote in-growth ofimplants.

A further object of the invention concerns the use of the calcium saltsor composite materials comprising them according to the invention, andespecially those composite materials having a protein component selectedfrom collagen, casein or gelatins, especially preferably gelatins ofTypes A, B or AB, particularly gelatin of the acid bone type, forprotection and/or for therapeutic and/or preventive treatment of teethand/or bones before or after injuries due to external influences,especially physiological, chemical, physical and/or microbiological innature, especially for prevention and repair of erosions of bones andteeth, especially dental enamel, care of the dental enamel, and forprotection of the teeth from attacks by acids, especially those due tobacterial activity or action of acids from foods, for protection againstdemineralization of the teeth, for sealing fissures, to protect againstand/or to repair primary lesions and/or initial caries in the dentalenamel and to smooth the surfaces of the teeth, to prevent caries, toimprove the ability to clean, the mechanical resistance of the teeth,and general dental health.

According to a preferred embodiment, the calcium salts according to theinvention, and preferably the composite materials comprising them,especially those composite materials having a protein component selectedfrom collagen, casein or gelatins, especially preferably gelatins ofTypes A, B or AB, particularly gelatin of the acid bone type, are usedagainst attacks by acids.

The term “acids” is understood here to mean both the intrinsic acids andthe extrinsic acids. Damage from intrinsic acids concerns particularlymedically related clinical pictures involving contact of the oral regionwith stomach acid, particularly in case of expulsion, regurgitation,heartburn, or vomiting, and also in relation to pathological eatingdisturbances, such as bulimia, in particular.

Use in case of attack by extrinsic acids, particularly those due tobacterial activity or action of acids from foods, is particularlysuitable.

It has also been observed that in addition to prevention of erosion ofteeth (dentine and enamel) and bones, there is also repair of erosionson teeth and bones, especially of the enamel, due to the compositematerials according to the invention.

The calcium salts according to the invention, and preferably thecomposite materials comprising them, particularly those compositematerials having a protein component selected from collagen, casein orgelatins, especially preferably gelatins of Types A, B or AB,particularly gelatin of the acid bone type, are therefore also usabletherapeutically to repair damages, especially erosions, of bones andteeth, particularly of enamel.

Preferably the calcium salts according to the invention, and preferablythe composite materials comprising them, particularly those compositematerials having a protein component selected from collagen, casein orgelatins, especially preferably gelatins of Types A, B or AB,particularly gelatin of the acid bone type, are used to protect againstand/or to repair primary lesions and/or initial caries in the dentalenamel and to seal fissures. According to the invention, fissures (thatis, crack-like intrusions on the chewing surfaces of the premolars andmolars) can be sealed, so that their susceptibility to caries isreduced.

Furthermore, use of the calcium salts according to the invention, andpreferably the composite materials comprising them, particularly thosecomposite materials having a protein component selected from collagen,casein or gelatins, especially preferably gelatins of Types A, B or AB,particularly gelatin of the acid bone type results in better mechanicalresistance, especially such that the extent of microcracks,microcraters, or mechanical abrasion is reduced.

The use according to the invention leads to better resistance tomechanical stress on the teeth, which can be caused not only by chewingbut also, in particular, by vigorous brushing. Damage or removal ofsoftened enamel can be avoided in this manner.

Because of the stated positive properties of the sparingly water-solublecalcium salts and/or the composite materials comprising them, especiallyof the composite materials, particularly those composite materialshaving a protein component selected from collagen, casein or gelatins,especially preferably gelatins of Types A, B or AB, particularly gelatinof the acid bone type, they themselves or compositions containing themcan thus be used generally to improve the ability to clean the teeth andto improve dental health in general.

The compositions for cleaning and care of the teeth can, for example, bein the form of pastes, liquid creams, gels or mouth washes. Thecomposite materials according to the invention distribute themselveseasily even in liquid preparations. They remain stable in dispersion anddo not tend to sediment.

The concentration of the sparingly water-soluble calcium salts orcomposite materials comprising them, preferably of the compositematerials, especially those having a protein component selected fromcollagen, casein or gelatins, especially preferably gelatins of Types A,B or AB, particularly gelatin of the acid bone type, in the oral anddental care materials according to the invention is 0.01 to 10% byweight, preferably 0.01 to 2% by weight, based on the total weight ofthe material.

The oral and dental care materials according to the invention can alsocontain 0.1 to 9% by weight, especially 2 to 8% by weight, of at leastone cleaning agent.

Cleaning agents are among the essential components of a toothpaste. Theyoccur alone or in combination with other cleaning agents or polishingagents, depending on their intended function. They provide mechanicalremoval of the uncalcified dental plaque and should ideally result inpolishing of the tooth surface (polishing action) with simultaneousminimal scrubbing (abrasive action) and damage to the enamel anddentine. The abrasive action of the polishing agents and cleaningmaterials is determined essentially by their hardness, particle sizedistribution and surface structure. In selection of suitable cleaningmaterials, accordingly, those with high cleaning power and minimalabrasive action are preferred.

Substances with small particle sizes, largely free of sharp corners andedges, with hardness and mechanical properties that do not excessivelystress the tooth or the tooth substance are used predominantly ascleaning materials at present.

Water-insoluble inorganic substances are usually used as cleaningmaterials or polishing agents. It is particularly advantageous to usevery finely divided polishing agents having a mean particle size of1-200 μm, preferably 1-50 μm, and particularly 1-10 μm.

In principle, the polishing agents according to the invention can beselected from silicic acids, aluminum hydroxide, aluminum oxide,silicates, organic polymers, or mixtures of those. The materialsaccording to the invention can also contain the metaphosphates, alkalineearth metal carbonates or bicarbonates, and calcium-containing polishingcomponents.

It can be preferred according to the invention to use silicic acids aspolishing agents in toothpastes or liquid tooth-cleaning materials. Onedistinguishes among the silicic acid polishing agents, basically betweengel silicic acids, hydrogel silicic acids and precipitation silicicacids. Precipitation and gel silicic acids are especially preferredaccording to the invention, as they can be varied widely in theirproduction and are particularly compatible with fluoride agents. Theyare also particularly suitable for the production of gel or liquid toothcreams.

Gel silicic acids are produced by reaction of sodium silicate solutionswith strong aqueous mineral acids, forming a hydrosol, aging to thehydrogel, washing and subsequent drying. If drying is done under gentleconditions to water contents of 15 to 35% by weight, the hydrogelsilicic acids such as those described in U.S. Pat. No. 4,153,680 areobtained. On drying of these hydrogel silicic acids to water contentsbelow 15% by weight, the previously open structure shrinks to the densestructure of the “xerogel.” Such xerogel silicic acids are known fromU.S. Pat. No. 3,538,230, for example.

The precipitation silicic acids are a second and preferably suitablegroup of silicic acid polishing agents. They are obtained byprecipitating silicic acid from dilute alkali silicate solutions byadding strong acids under conditions such that aggregation to the soland gel cannot occur. Suitable processes for producing precipitationsilicic acids are described, for example, in German Laid-OpenApplications 25 22 586 and 31 14 493. A precipitation silicic acidproduced according to German Laid-Open Application 31 14 193 isparticularly suitable according to the invention. It has a BET surfacearea of 15-110 m²/g, a particle size of 0.5 to 20 μm, in which at least80% by weight of the primary particles should be below 5 μm, and aviscosity in 30% glycerol-water (1:1) dispersion of 30-60 Pa S (20° C.).It is used at a proportion of 10-20% by weight in the toothpaste.Preferred suitable precipitation silicic acids of this type also haverounded corners and edges. They are obtainable, for example, fromDegussa under the tradename Sident® 12 DS.

Other precipitation silicic acids of this type are Sident® 8 fromDegussa and Sorbosil® AC 39 from Crosfield chemicals. These silicicacids are characterized by lower thickening action and a somewhatgreater mean article size of 8-14 μm with a specific surface of 40-75m²/g (by BET). They are particularly suitable for liquid tooth creams.They are reported to have a viscosity of 10-100 Pa S (25° C., shear rateD=10 s⁻¹).

Silicic acids of the Zeodent® type from Huber Corp., Tixosil® fromRhodia, and other Sorbosil types can also be used in the materialsaccording to the invention. Zeodent®113, Tixosil® 123 and Sorbosil® AC39are particularly preferred.

Toothpastes, on the other hand, having a distinctly higher viscositygreater than 100 Pa S (25° C., D=10 s⁻¹), require a sufficiently highproportion of silicic acids having particle sizes of less than 5 u,preferably at least 3% by weight of a silicic acid having a particlesize of 1 to 3 μm. It is preferable to add, along with the precipitationsilicic acids mentioned, even more finely divided, “thickening silicicacids” with a BET surface of 150-250 m²/g. Sipernat® 22 LS or Sipernat®320 DS from Degussa must be mentioned as examples of commercial productsthat meet the specified conditions.

A weakly calcined alumina having a content of α- and γ-aluminum oxidesin a proportion of about 0.01 to 5% by weight, preferably 0.1 to 2% byweight, based on the total weight of the material, is preferablysuitable as an aluminum oxide polishing agent.

Suitable weakly calcined aluminas are produced from aluminum hydroxideby calcining. On calcining, aluminum hydroxide converts tothermodynamically stable α-Al₂O₃ at temperatures above 1200° C. Thethermodynamically unstable Al₂O₃ modifications that appear attemperatures between 400 and 1,000° C. are called gamma forms (seeUllmann, Enzyclopädia der technischen Chemie [Encyclopedia of IndustrialChemistry], Vol. 7, page 298). One can adjust the degree of calcination,i.e., the conversion to the thermodynamically stable α-Al₂O₃, to anydesired level by selecting the temperature and duration of thecalcination. By weak calcination, one gets an alumina with a content ofγ-Al₂O₃ that decreases with increasing calcination temperature andlonger calcination duration. Weakly calcined aluminas differ from pureα-Al₂O₃ in having lower hardness of the agglomerates, greater specificsurface and greater pore volumes.

The dentine abrasion (RDA) of the more weakly calcined aluminas with10-50% by weight of γ-Al₂O₃, which are to be used according to theinvention, is only 30-60% of that for a strongly calcined pure α-Al₂O₃(measured in a standard toothpaste with 20% by weight alumina as thesole polishing agent).

In contrast to α-Al₂O₃, the γ-Al₂O₃ can be stained red with an aqueousammoniacal solution of Alizarin S(1,2-dihydroxy-9,10-anthraquinone-4-sulfonic acid). One can choose thedegree of stainability as a measure of the degree of calcination or ofthe proportion of δ-Al₂O₃ in a calcined alumina: Place about 1 g Al₂O₃,10 ml of a solution of 2 g/L Alizarin S in water and 3 drops of a 10% byweight aqueous solution of NH₃ in a test tube and boil briefly. Thenfilter off the Al₂O₃, wash it and dry it. Evaluate it microscopically orcalorimetrically.

Suitable weakly calcined aluminas containing 10-50% by weight of γ-Al₂O₃stain pale to deep pink by this procedure.

Aluminum oxide polishing agents of various degrees of calcination,fineness of grind, and bulk density are commercially available, such asthe “polishing aluminas” from Giulini-Chemie or ALCOA.

A suitable preferred grade, “Polishing alumina P10 finest” has anagglomerate size of less than 20 μm, a mean primary crystallite size of0.5-1.5 μm, and a bulk density of 500-600 g/L.

Use of silicates as components of polishing materials can also bepreferred according to the invention. They are used particularly ascleaning agents in modern practice. Examples of silicates usableaccording to the invention include aluminum silicates and zirconiumsilicates. In particular, sodium aluminum silicate with the empiricalformula Na₁₂(AlO₂)₁₂(SiO₂)₁₂.7H₂O can be a suitable polishing agent, asis the synthetic Zeolite A, for example.

Examples of water-insoluble metaphosphates according to the inventioninclude in particular sodium metaphosphate, calcium phosphate, such astricalcium phosphate, calcium hydrogen phosphate, calcium hydrogenphosphate dihydrate and calcium pyrophosphate.

Magnesium carbonate, magnesium hydrogen phosphate, trimagnesiumphosphate or sodium bicarbonate can also be used as polishing materialsaccording to the invention, especially mixed with other polishingmaterials.

Another polishing material suitable for use in the oral and dental carematerials according to the invention is calcium phosphate dihydrate(CaHPO₄.2H₂O). Calcium phosphate dihydrate occurs naturally as brushite.It is commercially available as a polishing material at suitableparticle sizes of 1 to 50 μm).

Oral and dental care materials which contain in addition 0.1 to 10% byweight, preferably 0.1 to 5% by weight, and particularly 0.1 to 3% byweight, based in each case on the total weight of the material, of acomponent that promotes remineralization, are preferred according to theinvention.

In the materials according to the invention, the component promotingremineralization promotes remineralization of the dental enamel andclosing of dental lesions. It is selected from fluorides, ormicroparticulate phosphate salts of calcium such as calciumglycerophosphate, calcium hydrogen phosphate, hydroxyapatite,fluoroapatite, fluoride-dosed hydroxyapatite, dicalcium phosphatedihydrate and calcium fluoride. However, magnesium salts such asmagnesium sulfate, magnesium fluoride or magnesium monofluorophosphatealso have remineralizing action.

Magnesium salts are preferred components promoting remineralizationaccording to the invention.

Suitable embodiments of the oral and dental care materials according tothe invention are solid, liquid, or semiliquid toothpastes and toothgels.

According to a further preferred embodiment, the oral and dental carematerials according to the invention also contain toothpaste ingredientssuch as surfactants, moisture retention agents, binders, flavors andsubstances active against tooth and gum diseases.

Surface-active surfactants or surfactant mixtures are usually used toimprove cleaning action and foaming in the oral and dental carematerials according to the invention. They promote rapid and completedissolution and distribution of tooth cream in the oral cavity and atthe same time they support the mechanical removal of the dental plaque,especially at the places that are hard to reach with a toothbrush. Theyalso favor incorporation of water-insoluble substances, such as aromaticoils, stabilize the polishing material dispersion, and support theanti-caries action of fluorides.

Anionic, zwitterionic, ampholytic, nonionic and cationic surfactants ormixtures of them can, in principle, be used as surfactants in toothcream formulations. According to the invention, tooth creams preferablycontain at least one surfactant from the group of anionic surfactants.

The surfactant or mixture of surfactants is usually used in thepreparations according to the invention at a proportion of 0.1-10% byweight, preferably 0.3-7% by weight, and particularly 1-5% by weight,based on the total weight of the composition.

Anionic Surfactants.

Anionic surfactants are suitable surfactants with good foaming action.They also exhibit a certain enzyme-inhibiting action on the bacterialmetabolism of the dental plaque.

They include, for instance, alkali or ammonium salts, especially sodiumsalts, of C₈-C₁₈ alkanecarboxylic acids, of alkyl polyglycol ethersulfates having 12-16 C atoms in the linear alkyl group and 2-6 glycolether groups in the molecule, of linear alkane-(C₁₂-C₁₈)-sulfonates,sulfosuccinic acid monoalkyl (C₁₂-C₁₈) esters, sulfated fatty acidmonoglycerides, sulfated fatty acid alkanolamides, sulfoacetic acidalkyl-(C₁₂-C₁₆)-esters, acyl sarcosines, acyl taurides and acylisethionates, each having 8-18 C atoms in the acyl group.

Use of at least one anionic surfactant is preferred, especially a sodiumlauryl alkyl sulfate having 12-18 C atoms in the alkyl group. One suchsurfactant is sodium lauryl sulfate which is commercially available, forexample, as Texapon® K12 G.

Zwitterionic and Ampholytic Surfactants.

Use of zwitterionic and/or ampholytic surfactants, preferably combinedwith anionic surfactants, can be preferred according to the invention.Those surface-active compounds that have at least one quaternaryammonium group, at least one carboxylate, and one sulfonate group in themolecule are called zwitterionic surfactants. Particularly suitablezwitterionic surfactants are the so-betaines such asN-alkyl-N,N-dimethylammonium glycinate, such as trimethylammoniumglycinate, coco alkyl dimethylammonium glycinate,N-acylaminopropyl-N,N-dimethylammonium glycinates, such as cocoacylaminopropyl dimethylammonium glycinate and2-alkyl-3-carboxymethyl-3-hydroxyethylimidazoline, each having 8 to 18 Catoms in the alkyl or acyl group, and cocoacylaminoethyl hydroxyethylcarboxymethyl glycinate. The fatty acid amide derivative known by theCTFA name of cocamidopropyl betaine is especially preferred. Suchproducts are commercially available, for example, under the tradenamesof Tego-Betain® BL-215 and ZF 50, as well as Genagen® CAB.

Ampholytic surfactants are understood to be those surface-activecompounds that contain in the molecule not only a C₈-C₁₈ alkyl or acylgroup but also at least one free amino group and at least one —COOH or—SO₃H group and which are able to form internal salts. Examples ofsuitable ampholytic surfactants include N-alkylglycines,N-alkylpropionic acids, N-alkylaminobutyric acids,N-alkyliminodipropionic acids, N-hydroxyethyl-N-alkylamidopropylglycines, N-alkyltaurines, N-alkylsarcosines, 2-alkylaminopropionicacids and alkylaminoacetic acids, each having some 8 to 18 C atoms inthe alkyl group. N-cocolalkylaminopropionate,cocoacylaminoethylaminopropionate and C₁₂-C₁₈-acylsarcosine areespecially preferred ampholytic surfactants. Aside from the ampholyticsurfactants, quaternary emulsifiers can also be considered. Those of theesterquat type, preferably methyl-quaternized di-fatty acidtriethanolamine ester salts, are preferred.

Nonionic Surfactants.

Nonionic surfactants are particularly suited for supporting the cleaningaction according to the invention. Those nonionic surfactants that areselected from at least one of the following groups are particularlypreferred:

-   -   addition products of 2 to 30 moles of ethylene oxide and/or 0 to        5 moles of propylene oxide to linear fatty alcohols with 8 to 22        C atoms, to fatty acids with 12 to 22 C atoms and to alkyl        phenols with 8 to 15 C atoms in the alkyl group;    -   C₁₂-C₁₈ fatty acid monoesters and diesters of addition products        of 1 to 30 moles of ethylene oxide to glycerol;    -   glycerol monoesters and diesters and sorbitan monoesters and        diesters of saturated and unsaturated fatty acids having 6 to 22        carbon atoms, and their ethylene oxide diesters and sorbitan        monoesters and diesters of saturated and unsaturated fatty acids        having 6 to 22 carbon atoms, and their ethylene oxide addition        products;    -   alkyl monoglycosides and oligoglycosides having 8 to 22 carbon        atoms in the alkyl group and their ethoxylated analogs;    -   Addition products of 15 to 60 moles of ethylene oxide to castor        oil and/or hardened castor oil;    -   polyol esters and especially polyglycerol esters such as        polyglycerol polyricinoleate, polyglycerol        poly-12-hydroxystearate or polyglycerol dimerate.

Mixtures of compounds from more than one of these substance classes arealso suitable;

-   -   addition products of 2 to 15 moles of ethylene oxide to castor        oil and/or hardened castor oil;    -   partial esters based on linear, branched, unsaturated or        saturated C₆-C₂₂ fatty acids, ricinoleic acid and        12-hydroxystearic acid and glycerol, polyglycerol,        pentaerythritol, dipentaerythritol, sugar alcohols (such as        sorbitol), sucrose, alkyl glucosides (such as methyl glucoside,        butyl glucoside, or lauryl glucoside) and polyglucosides (such        as cellulose);    -   mono, di, and tri-alkyl phosphates and mono, di and/or        tri-PEG-alkyl phosphates and their salts;    -   wool alcohols;    -   polysiloxane-polyalkyl-polyether copolymers or corresponding        derivatives;    -   mixed esters of pentaerythritol, fatty acids, citric acid and        fatty alcohol according to German Patent 1165574 and/or mixed        esters of fatty acids having 6 to 22 carbon atoms, methylglucose        and polyols, preferably glycerol or polyglycerol, and    -   polyalkylene glycols.

The addition products of ethylene oxide and/or propylene oxide to fattyalcohols, fatty acids, alkylphenols, glycerol monoesters and diesters,and sorbitan monoesters and diesters of fatty acids or to castor oil areknown products that are commercially available and are preferredaccording to the invention. These are mixtures of homologs with anaverage degree of alkoxylation equivalent to the ratio of the quantitiesof ethylene oxide and/or propylene oxide and substrate with which theaddition reaction was carried out. C₁₂-C₁₈ fatty acid monoesters anddiesters of addition products of ethylene oxide to glycerin are knownfrom German Patent 2024051 as fat-replacement agents for cosmeticpreparations.

C₈-C₁₈-alkyl monoglycosides and oligoglycosides, their production, andtheir use are known from the state of the art, for example, from U.S.Pat. No. 3,839,318, DE-A-20 36 472, EP-A-77 167 OR WO A-93/10132. Theyare produced principally by reacting glucose or oligosaccharides withprimary alcohols having 8 to 18 C atoms. With respect to the glycosidegroup, both monoglycosides, in which a cyclic sugar group is boundglycosidically to the fatty alcohol and oligomeric glycosides with adegree of oligomerization up to preferably about 8 are suitable. Herethe degree of oligomerization is a statistical average based on theusual homolog distribution for such industrial products. Analkyl-(oligo)-glycoside of the formula RO(C₆H₁₀O)_(x)—H in which Rrepresents an alkyl group with 12 to 14 C atoms and x is an average of 1to 4 is preferably suitable as the oligoglycoside.

PEG-glyceryl stearate must be mentioned as a particularly preferredexample of a usable nonionic surfactant. It is commercially availableunder the name Tagat®.

Moisture retention agents are usually used in dental cosmetics toprotect against drying and to control the consistency and cold stabilityof the products. They can also be used as suspending agents and toinfluence taste and shine.

Toxicologically unobjectionable polyols such as sorbitol, xylitol,glycerol, mannitol, 1,2-propylene glycol or mixtures of those areusually used as moisture retention agents. Polyethylene glycols withmolecular weights of 400-2,000 can also serve as moisture retentioncomponents in tooth creams.

A combination of multiple moisture retention components is preferred,with the combination of glycerol and sorbitol containing 1,2-propyleneglycol or polyethylene glycol is considered especially preferred.

Depending on the type of product, the complete composition contains themoisture retention agent, or the mixture of moisture retention agents ina proportion of 10-85% by weight, advantageously 15-70% by weight, andparticularly 25-50% by weight.

In a preferred embodiment, the materials according to the invention alsocontain at least one binder or thickener. These act to control theconsistency and further inhibit the separation of the liquid and solidingredients.

They are used in the compositions according to the invention atproportions of 0.1-5% by weight, preferably 0.1-3% by weight, andespecially 0.5-2% by weight.

For example, natural and/or synthetic water-soluble polymers such asalginates, carrageenans, agar-agar, guar gum, gum arabic, succinoglycangum, guar meal, St. John's bread nut meal, tragacanth, karaya gum,xanthan, pectins, cellulose, and their ionic and nonionic derivativessuch as carboxymethylcellulose, hydroxyethylcellulose ormethylhydroxypropyl cellulose, hydrophobically modified celluloses,starches and starch ethers are used according to the invention.

Water-soluble carboxyvinyl polymers (e.g., Carbopol® types), polyvinylalcohol, polyvinylpyrrolidone and higher-molecular-weight polyethyleneglycols (especially those having molecular weights of 10²-10⁶ Dalton)are also suitable as binders or thickeners. Laminar silicates and finelydivided silicic acids (aerogel silicic acids and pyrogenic silicicacids) can also fulfill this function.

In a further preferred embodiment, the oral and dental cleaning materialcontains other agents active against tooth and gum disease. Those activeagents are understood to include, according to the invention, anticariesagents, antimicrobial agents, calculus inhibitors, flavoring materialsor an arbitrary combination of those substances.

Anticaries Agents.

Fluorine compounds, preferably from the group of fluorides ormonofluorophosphates in a proportion of 0.1-0.5% by weight, areparticularly suitable for combating and preventing caries. Suitablefluorine compounds include, for example, sodium fluoride, potassiumfluoride, tin fluoride, disodium monofluorophosphate (Na₂PO₃F),dipotassium monofluorophosphate, or fluoride from an organic aminocompound.

Anti-Plaque Agents.

Preferred preparations according to the invention, especially oral anddental care and cleaning materials, are characterized in that they alsocontain anti-plaque agents, preferably p-hydroxybenzoic acid methyl,ethyl, or propyl esters, sodium sorbate, sodium benzoate,bromchlorophen, Triclosan, phenylsalicylic acid esters, biguanides suchas chlorhexidine, thymol, preferably in proportions of 0.1 to 5% byweight, preferably of 0.25 to 2.5% by weight, and particularly 0.5 to1.5% by weight, based in each case on the complete material.

Antimicrobial Agents.

Phenols, resorcinols, bisphenols, salicylanilides and salicylamides, aswell as their halogenated derivatives, halogenated carbanilides andp-hydroxybenzoic acid esters are suitable antimicrobial agents.

Of the antimicrobial components, the particularly suitable ones arethose that inhibit the growth of plaque bacteria. For example,halogenated diphenyl ethers such as 2,4-dichloro-2′-hydroxydiphenylether, 4,4′-dichloro-2′-hydroxydiphenyl ether,2,4,4′-tribromo-2′-hydroxydiphenylether, and2,4,4′-trichloro-2′-hydroxydiphenyl ether (Triclosan) are suitableantimicrobial agents. Along with bromchlorphen, bis-biguanides such aschlorhexidine and alexidine, phenylsalicylic acid esters and5-amino-1,3-bis(2-ethylhexyl)-hexahydro-5-methylpyrimidine (Hexetidine),zinc and copper ions also have antimicrobial action, with synergisticeffects occurring, particularly in combination with Hexetidine andTriclosan. Quaternary ammonium compounds such as cetylpyridiniumchloride, benzalkonium chloride, domiphen bromide and dequaliniumchloride are also usable. Octapinol, octenidine and sanguinarin havealso proved to be antimicrobially active.

The antimicrobial agents are used preferably in proportions of 0.01-1%by weight in the materials according to the invention. It isparticularly preferred to use Irgacare® MP in a proportion of 0.01-0.3%by weight.

Calculus Inhibitors.

Calculus is made up of mineral deposits that are very similar to thenatural tooth enamel. To inhibit calculus formation, substances thatinhibit formation of crystallization nuclei are added to the toothcleaning substances according to the invention. They inhibit furthergrowth of nuclei that are already present. They include, for instance,condensed phosphates, preferably selected from the group oftripolyphosphates, pyrophosphates, trimetaphosphates or mixtures ofthem. They are used as their alkali or ammonium salts, preferably astheir sodium or potassium salts. Aqueous solutions of these phosphatestypically have an alkaline reaction, so that the pH of the dental carematerials according to the invention is optionally adjusted to 7.5-9 byaddition of acid. Examples of acids that can be used include citricacid, phosphoric acid, or acid salts, such as NaH₂HPO₄. The desired pHof the dental care material can also be adjusted by adding acid salts ofthe condensed phosphates, such as K₂H₂P₂O₇.

Mixtures of various condensed phosphates and/or hydrated salts of thecondensed phosphates are usable according to the invention. Calculusinhibitors are usually used in proportions of 0.1-5% by weight,preferably 0.1-3% by weight, and particularly 0.1-2% by weight in thematerials according to the invention.

Organophosphates such as 1-azacycloheptane-2,2-diphosphonate (sodiumsalt), 1-hydroxyethane-1,1-diphosphonate (sodium salt) and zinc citrateare other suitable calculus inhibitors.

Agents Against Hypersensitive Teeth.

The materials according to the invention preferably also contain agentsagainst hypersensitive teeth. They are selected from potassium andstrontium salts such as potassium chloride, potassium sulfate, potassiumbicarbonate, potassium citrate, potassium acetate, potassium nitrate,strontium chloride, strontium nitrate, strontium citrate, strontiumacetate, strontium lactate and Eugenol.

Oral and dental care materials can contain Eugenol mixed with aromaticoils. It is preferable for the compositions to contain it in the form ofoil of clove bud.

The oral and dental care materials according to the invention preferablycontain at least 0.5% by weight of potassium or strontium ions in theform of a dissolved salt and at least 0.01% by weight Eugenol in thepure form or in the form of oil of clove bud.

Flavoring Materials.

The materials according to the invention preferably contain flavoringmaterials, including, for example, sweeteners and/or preferably containflavoring materials, including, for example, sweeteners and/or aromaticoils.

Suitable sweeteners are, for example, saccharinates (especially sodiumsaccharin), cyclamates (especially sodium cyclamate) and sucrose,lactose, maltose or fructose.

All the natural and synthetic fragrances can be considered as fragranceoils for oral and dental care materials. Natural fragrances can be usedboth in the form of the ethereal oil (mixture) isolated from the plantsas well as in the form of the individual components isolated from themixture. It is preferred that there be at least one aromatic oil fromthe group of peppermint oil, curled mint oil, anise oil, Indian aniseoil, caraway oil, eucalyptus oil, fennel oil, cinnamon oil, clove oil,geranium oil, sage oil, allspice oil, thyme oil, marjoram oil, basiloil, citrus oil, wintergreen oil, or one or more components of theseoils that are isolated from them or produced synthetically. The mostimportant components of the oils named are, for example, menthol,carvone, anethol, cineol, eugenol, cinnamaldehyde, caryophyllene,geraniol, citronellol, linalool, salven, thymol, terpinenes, terpinol,methylchavicol and methyl salicylate. Examples of other suitablefragrances are menthyl acetate, vanillin, ionone, linalyl acetate,rhodinol and piperitone.

Finally, the oral and dental care materials can contain other usualadditives to improve the stability and sensory properties. Examples ofsuch additives are:

-   -   Vitamins, such as retinol, biotin, tocopherol, ascorbic acid and        their derivatives (e.g., esters, salts);    -   Pigments, such as titanium dioxide or zinc oxide;    -   Colored pigment particles, such as colored silicic acid        particles, such as are in commerce under the tradenames        Sorbosil® BFG 51, BFG 52 and BFG 53, or Sorbosil® 2352. Mixtures        of differently colored pigment particles can also be used. The        materials according to the invention can contain such gel        silicic acid particles, colored strongly orange, red or blue,        for example, in proportions of 0.1-1.0% by weight.    -   Bleaches, such as hydrogen peroxide and hydrogen peroxide        precursors;    -   Dyes;    -   pH-adjusting agents and buffers, such as sodium citrate, sodium        bicarbonate or potassium and sodium phosphates;    -   Preservatives, such as p-hydroxybenzoic acid methyl, ethyl, or        propyl ester, sodium sorbate, sodium benzoate, bromchlorophen or        Triclosan;    -   Wound-healing and anti-inflammatory substances such as        allantoin, urea, panthenol, azulene or chamomile extract,        acetylsalicylic acid derivatives or alkali rhodanides;    -   Mineral salts such as zinc, magnesium and manganese salts, e.g.,        sulfates.

The materials according to the invention contain all these optionaltoothpaste ingredients in proportions of about 2 to 10% by weight, basedon the total weight. Preparations to be used according to the invention,preferably oral and dental care agents, especially toothpastes, can alsocontain substances that reduce the sensitivity of the teeth, such aspotassium salts, e.g., potassium nitrate, potassium citrate, potassiumchloride, potassium bicarbonate and potassium oxalate. Oral and dentalcare and cleaning agents preferred according to the invention arecharacterized by containing substances that reduce the sensitivity ofthe teeth, preferably potassium salts, especially preferably potassiumnitrate and/or potassium citrate and/or potassium chloride and/orpotassium bicarbonate and/or potassium oxalate, preferably inproportions of 0.5 to 20% by weight, especially preferably of 1.0 to 15%by weight, further preferably of 2.5 to 10% by weight, and especially of4.0 to 8.0% by weight, based in each case on the total agent.

Preparations, especially oral and dental care and cleaning agents arefurther preferred which contain substances reducing the sensitivity ofthe teeth, preferably potassium salts, especially preferably potassiumnitrate and/or potassium citrate and/or potassium chloride and/orpotassium bicarbonate and/or potassium oxalate, preferably inproportions of 0.5 to 20% by weight, especially preferably of 1.0 to 15%by weight, further preferably of 2.5 to 10% by weight, and especially of4.0 to 8.0% by weight, based in each case on the total means.

Oral and dental care and cleaning agents to be used according to theinvention are especially preferably characterized by containing 0.2 to20% by weight, preferably 0.4 to 14% by weight, especially preferably0.5 to 3% by weight and particularly 0.6 to 2% by weight of at least onebioactive glass.

The oral and dental care and cleaning agents to be used according to theinvention, of this embodiment, contain bioactive glass or glass powderor glass ceramic powder or composite materials comprising such abioactive glass. In the context of the present application ‘glasspowder’ is understood to mean also granulations and glass beads.

Because of the requirements for the toxicologic acceptability of theglass and its suitability for consumption, the glass powder must beparticularly pure. The heavy metal loading is preferably very slight.For instance, the maximum concentrations in the area of cosmeticformulations are preferably: for Pb<20 ppm, Cd<5 ppm, As<5 ppm, Sb<10ppm, Hg<1 ppm, Ni<10 ppm.

The unceramized starting glass which is contained directly in thepreferred compositions according to the invention, or is optionally usedto produce a glass ceramic usable according to the invention containsSiO₂ as the network former, preferably between 35 and 80% by weight. Atlow concentrations the tendency to spontaneous crystallization increasessharply and the chemical resistance decreases. At high SiO₂ values, thecrystallization stability can decrease and the processing temperaturebecomes distinctly elevated, with poorer hot forming properties. Na₂O isused as a flux to melt the glass. The effect on the melting is bad atconcentrations below 5%. Sodium is a component of the phases that formon ceramizing and it must be at correspondingly high concentration inthe glass if highly crystalline phases are to be produced by ceramizing.K₂O acts as a flux for melting the glass. Potassium is also released inaqueous systems. If the potassium concentration in the glass is high,potassium-containing phases such as potassium silicates also separate.In silicate glasses, glass ceramics or composites, the chemicalresistance of the glass and thus the release of ions into aqueous media,can be adjusted by the P₂O₅ content. In phosphate glasses, P₂O₅ is thenetwork former. The P₂O₅ is preferably between 0 and 80% by weight. Toimprove the fusibility, the glass can contain up to 25% by weight B₂O₃.Al₂O₃ is used to adjust the chemical resistance of the glass.

The glass ceramic can contain ions with antimicrobial action, such asAg, Au, I, Ce, Cu, or Zn at concentrations below 5% by weight toincrease the antimicrobial, especially the antibacterial, properties ofthe glass ceramic.

Ions that provide color, such as Mn, Cu, Fe, Cr, Co or V, can becontained individually or in combination, preferably at a totalconcentration of less than 1% by weight.

The glass or glass ceramic is usually used in powder form. Theceramizing can be accomplished either with a glass block or glassribbons, or with glass powder. After the ceramizing, the glass ceramicblocks or ribbons must be ground to powder. If the powder was ceramized,is may optionally be reground to remove aggregates formed during theceramizing step. The grindings can be done dry or in aqueous ornonaqueous grinding media. The particle sizes are usually less than 500μm. Particle sizes of <100 μm or <20 μm have proven favorable. Particlesizes <10 μm, and less than 5 μm and less than 2 μm are particularlysuitable; see below.

The bioactive glasses or glass powders or glass ceramic powders orcomposite compositions contained in the preferred compositions accordingto the invention comprise glasses which preferably comprise thefollowing components: SiO₂: 35-80% by weight; Na₂O: 0-35% by weight;P₂O₅: 0-80% by weight; MgO: 0-5% by weight; Ag₂O: 0-0.5% by weight; Agl:0-0.5% by weight; NaI: 0-5% by weight; TiO₂: 0-5% by weight; K₂O: 0-35%by weight; ZnO: 0-10% by weight; Al₂O₃: 0-25% by weight; and B₂O₃: 0-25%by weight.

Ions such as Fe, Co, Cr, V, Ce, Cu, Mn, Ni, Bi, Sn, Ag, Au, or I,individually or together, in a total of up to 10% by weight, can beadded to the basic glass of the composition above to attain othereffects such as coloration of UV filtration. A further glass compositioncan be as follows: SiO₂: 35-80% by weight; Na₂O: 0-35% by weight; P₂O₅:0-80% by weight; MgO: 0-5% by weight; Ag₂O: 0-0.5% by weight; Agl:0-0.5% by weight; NaI: 0-5% by weight; TiO₂: 0-5% by weight; K₂O: 0-35%by weight; ZnO: 0-10% by weight; Al₂O₃: 0-25% by weight; B₂O₃: 0-25% byweight; SnO: 0-5% by weight; CeO₂: 0-3% by weight; and Au: 0.001-0.1% byweight.

Especially preferred oral and dental care and cleaning agents arecharacterized in that the bioactive glass has the following composition,based on its weight:

SiO₂ 35 to 60% by weight preferably 40 to 60% by weight Na₂O  0 to 35%by weight preferably 5 to 30% by weight K₂O  0 to 35% by weightpreferably 0 to 20% by weight P₂O₅  0 to 10% by weight preferably 2 to10% by weight MgO  0 to 10% by weight preferably 0 to 5% by weight CaO 0 to 35% by weight preferably 5 to 30% by weight Al₂O₃  0 to 25% byweight preferably 0 to 5% by weight B₂O₃  0 to 25% by weight preferably0 to 5% by weight iO₂  0 to 10% by weight preferably 0.1 to 5% by weight

As already noted above, the bioactive glass is preferably used inparticulate form. Here, specially preferred oral and dental care andcleaning agents are characterized in that the particle sizes of theantimicrobial glass are <10 μm, preferably 0.5 to 4 μm to 4 μm, andespecially preferably 1 to 2.

Toothpastes containing silicic acid, polishing agents, moistureretention agents, binders and fragrances, which contain 0.00001 to 10,especially 0.01 to 4% by weight, preferably 0.01 to 2% by weight of thecomposite materials according to the invention of nanoparticulatecalcium salts from the group of hydroxyapatite, fluoroapatite andcalcium fluoride are a preferred embodiment.

It is desirable, in use of the composite materials according to theinvention in products for daily oral and dental care, that the processof remineralization and neomineralization run particularly effectivelyand rapidly.

The composite materials according to the invention can be applied forcoating implants by standard processes of immersion coating or plasmaspraying, which are known to those skilled in the art.

The composite materials according to the invention can be combined withother suitable materials such as glycosaminoglycans or proteins for usead injectable bone replacement materials, and can be formulated withsuitable solvents and aids such as a dilute aqueous phosphate buffer.

A further object of the present invention concerns candies containingthe sparingly water-soluble calcium salts or composite materialscomprising them. Preferably at least 0.000001% by weight of at least onesparingly water-soluble calcium salt or composite materials comprisingit are contained.

It is particularly preferable for the candies, particularly thosedescribed below, to contain composite materials according to theinvention, of a sparingly water-soluble calcium salt according to theinvention and a protein component which is preferably selected fromcollagen, gelatins, casein, and hydrolysates of them, preferablygelatins, especially preferably gelatins of Type A, B or AB,particularly gelatin of the acid bone type.

According to a further preferred embodiment, the candy is selected fromthe group of confectioneries. Confectioneries are a manifold group offoods which, according to the Guideline for Confectioneries of theFederal Association of the German Confectioneries Industry, mostly havea strong sweet taste due to sugar and/or other common commercial typesof sugars, optionally sugar alcohols, sweeteners or other sweetingredients. Confectioneries are also fillings, glazes or candies, aswell as layers, coatings or fillings of confectioneries or fine bakedgoods. The confectioneries also include sugar-free confectioneries. Inthese, the sweet taste is produced by sugar alcohols and/or syntheticsweeteners.

Preferred confectioneries include in particular hard and soft caramels,gumdrops, jellies, foamed confectioneries, licorice products, coatedtablets, pastilles and candied fruits.

Caramels (also called bonbons) derive their unique nature from boilingdown a solution of sugars and/or sugar alcohols. They are made invarious forms, using materials that add taste and odor, or which providecolors, and/or which affect the nature, with or without filling. Thenature of the caramels ranges from hard caramels, i.e., drops, up tosoft caramels. They are distinguished particularly by their residualwater content. That can be up to about 5% by weight in hard caramels andup to about 15% by weight in soft caramels. Examples of soft caramelsare the elastic chewable gum-like starbursts or the soft, easilychewable, sometimes sticky, toffees. Bonbons differ by the manner oftheir production, such as cut, pressed, poured and layered bonbons.

Jellies, in the sense of the invention, are soft elastic sugar productswith consistency such that they can be bitten (e.g., gelled fruits).Gumdrops such as fruit gums, gummy bears, wine gummies, or gummypastilles are also sweeteners according to the invention. They areviscoelastic and chewable solids, and are produced just like the jelliesfrom sugars and/or sugar alcohols, gelling agents (such as agar, pectinor gum arabic), gelatins and/or starches (optionally modified). Waxes orvegetable oils can also be used as release agents and glossing agents.

Licorice products are made from a mixture of sugars and/or sugaralcohols, gelatins and/or (also modified) starches and/or flour and/orgelling and thickening agents and various fragrances. Licorice productsalso contain as a characteristic ingredient at least 3% licorice juice(Succhus liquiritiae; in the usual commercial dry form). Addition of upto 8% by weight, especially up to 2% by weight of sal ammoniac [ammoniumchloride] yields strong licorices.

Dragees [coated tablets] consist of a liquid, soft or solid core coveredwith a smooth or rippled coat made with sugars and/or sugar alcohols,chocolates, and/or other glazes in the sugar-coating process. In thesugar-coating process, for example, a fine spray of a saturated sugarsolution is sprayed from a nozzle onto the core, which rotating in acoating pan. Because of the hot air blown in at the same time, the sugarcrystallizes and slowly forms many thin layers around the core. If thesugar layer does not contain residual moisture, the candy is called ahard dragee. Soft dragees, on the other hand, can contain some 6 to 12%by weight, especially 8 to 10% by weight residual moisture. Dragees areoften given a thin non-sticking and glossing layer. The glossing layeris produced by treatment with wax-like substances, e.g., carnauba wax.In particular, substances influencing the nature, such as starches andcolors giving colors, taste and flavor are used.

Pressings or pastilles are produced in the tableting or powder-castingor extrusion process. They optionally contain small amounts of bindersand lubricants along with the sugars and/or sugar alcohols.

According to a particularly preferred embodiment, the candy is a hard orsoft caramel or a dragee. These sweeteners have the advantage that theyare retained in the mouth for a long time and the calcium salt orcomposite material in the sweet is released only gradually. Thatparticularly promotes and mineralizing and especially theneomineralizing effect.

The active substance can advantageously be incorporated directly in themelt for candies made from melts of sugar and/or sugar alcohols.Surprisingly, the sugar does not crystallize in the melt, giving apolycrystalline mass that is difficult to work when the usual groundapatite is added. The sandy taste that comes with coarse-grained apatitecould also not be detected.

The hard caramels, such as bonbons, drops, candy sticks or lollipops,that stay in the mouth for a particularly long time, are particularlypreferred. That results in the optimal stepwise release of the calciumsalt or composite material according to the invention.

Although some of the ingredients (sugars) damage teeth, consumption ofthe candy according to the invention results in not only the pleasurableexperience but also tooth care and tooth preservation, and furthermoreto mineralization of the enamel and/or of the dentine. The tooth care,usually with a toothbrush, tooth paste and/or mouth wash, which has inthe past been necessary, but which is not always possible after enjoyingsweets, can thus be omitted without damage to the teeth due to theconsumption of sweets.

Sorbitol syrup, mannitol, xylitol, lactitol, isomaltitol, maltitol ormaltitol syrup are sugar alcohols preferred according to the invention.The substances have the advantage that they have fewer calories per 100g, and also the degradation of the sugar alcohols to acids by somebacterial of the oral cavity is so slow that they have no cariogenicaction. The addition, according to the invention, of composite materialsaccording to the invention to candies containing sugar substitutesresults in mineralization of the teeth during and/or after enjoying thesweet, and so contributes particular to maintenance of healthy teeth.

According to another preferred embodiment, the candy according to theinvention is filled. Candies with a solid, gel, or liquid core allow,among other things, addition of other taste components in that core.Likewise, active ingredients that cannot be incorporated directly (as bymixing) without reduction or loss of the effect can be added in thismanner. Vitamins or alcohol, among other things, can be incorporated insuch fillings in bonbons.

It is particularly preferred that the filling contain the calcium saltsaccording to the invention and/or composite materials comprising them.The material according to the invention that is contained in the fillingcan also be incorporated into sweets in which there is a danger of lossof the effect due to the properties of the candy or its production. Thisfilling can, in particular, be a suspension, a gel or a syrup. Inparticular, the suspensions or gels can be made with a water base toassure good compatibility. Addition of dispersing or wetting agentssuitable for food use can serve to hold the composite materialsaccording to the invention in the suspension. Organic thickeners andtheir derivatives, in particular, are suitable gel-formers.

Aside from synthetic organic thickeners, natural organic thickeners areparticularly suitable. They include in particular agar-agar,carrageenan, tragacanth, gum arabic, alginates, pectins, polyoses, guarmeal, St. John's bread nut meal, starches, dextrins, gelatins andcasein. Modified natural products are likewise preferred, especiallycarboxymethylcellulose and other cellulose ethers, hydroxyethylcelluloseand hydroxypropylcellulose, as well as nutmeal ethers. Synthetic organicthickeners such as polyethers or inorganic thickeners such aspolysilicic acids and/or clay minerals (e.g., montmorillonite, zeolitesor silicic acids) can likewise be used according to the invention.

According to a further embodiment of the present invention the candy isa chewing gum.

The chewing gum also promotes flow of saliva because of the chewingmotion. The acids that cause caries are diluted and so the health of theoral cavity is supported in a natural manner. Chewing gums thatparticularly provide tooth care and preservation contain sugarsubstitutes, especially sugar alcohols.

Chewing gums comprise sugars and/or sugar alcohols, sweeteners,fragrances, other additives providing odor, taste and consistency, dyes,and a water-insoluble chewing mass that becomes plastic on chewing. Thechewing gums may also contain release and coating agents (such as talc).

Chewing masses are mixtures of substances providing consistency, i.e.,the natural gums, which are solidified saps (exudates) of tropicalplants such as chicle, gum arabic, gutta percha, karaya gum, tragacanth,rubber, and the thermoplastic synthetics, butadiene-styrene copolymers,isobutylene-isoprene copolymers, polyethylene, polyisobutylene,polyvinyl esters of the unbranched fatty acids from C₂ to C₁₈ andpolyvinyl ethers.

Resins and balsams are used as plasticizers. The natural substancesinclude benzoin, dammar, colophonium, mastic, myrrh, olibanum, perubalsam, sandarac, shellac and tolu balsam. The synthetics includecoumarone-indene resin, glycerol-pentaerythritol esters of the resinacids of colophonium and their hydrogenation products.

Paraffins (natural and synthetic) and waxes are used to influence theelasticity. The waxes include those of plant origin such as carnauba waxand those of animal origin such as beeswax or wool wax. There are alsomineral waxes such as microcrystalline waxes, as well as chemicallymodified or synthetic waxes. Emulsifiers (e.g., lecithins or mono- anddi-glycerides of acids of cooking fat) and esters such as glycerylacetate and even glycerin are used as plasticizers.

Vegetable hydrocolloids such as agar-agar, alginic acid and alginates,guar nut meal, St. John's bread nut meal or pectin are added to regulatethe consistency of the chewing mass. Fillers, calcium or magnesiumcarbonates, oxides, such as aluminum oxide, silicic acid and calcium ormagnesium silicates, are used to adjust the chewing properties ofchewing masses. Stearic acid and its calcium and magnesium salts areused to reduce sticking of the chewing mass to the tooth enamel.

Before the remaining ingredients required to make chewing gum are mixedin, it is necessary to heat the chewing mass, which amounts to about20-35% (but at least 15%) of the finished chewing gum, to 50-60° C.

According to a particularly preferred embodiment of the presentinvention, the chewing gum is enveloped by at least one layer, whichcomprises at least one calcium composite material according to theinvention.

The composite materials are simply added to the chewing mass to makechewing gum according to the invention. Alternatively, according to theinvention, it is also possible to make a coated chewing gum, with whichthe enveloping layer contains the two essential ingredients of theproduct according to the invention. To produce such coated chewing gumsaccording to the invention, the active ingredients, that is, the calciumsalt and/or its composite, simply a solution and/or dispersion fromwhich the coating is made, are added and stirred in.

In a preferred embodiment of the present invention the chewing gumaccording to the invention contains sugar. In connection with thepresent invention, “sugar” or “sugars” are understood to be productssuch as sucrose, purified crystalline sucrose, for instance in the formof refined sugar, raffinates, refined white sugar, white sugar orsemi-white sugar, aqueous solutions of sucrose, such as in the form ofliquid sugar, aqueous solutions of sucrose partially inverted byhydrolysis, such as invert sugar, syrup or invert liquid sugar, glucosesyrup, dried glucose syrup, hydrates of dextrose, anhydrous dextrose andother products of starch saccharification, as well as trehalose,trehalulose, tagatose, lactose, maltose, fructose, leucrose,isomaltulose (palatinose), condensed palatinose and hydrated condensedpalatinose. Thus the sugar-containing chewing gum according to theinvention is characterized in that either the chewing gum itself or thecoating layer, or both contains, as sweeteners, sucrose, liquid invertsugar, invert sugar syrup, glucose, glucose syrup, polydextrose,trehalose, trehalulose, tagatose, lactose, maltose, fructose, leucrose,isomaltu lose (palatinose), condensed palatinose and hydrated condensedpalatinose or mixtures of those. The sugar-containing chewing gumaccording to the invention can also contain, aside from the sugar typesmentioned above, sugar substitutes, especially sugar alcohols such aslactitol, sorbitol, xylitol, mannitol, maltitol, erythritol,6-O-α-D-glycopyranosyl-D-sorbitol (1,6-GPS),1-O-α-D-glucopyranosyl-D-sorbitol (1,1-GPS),1-O-α-D-glucopyranosyl-D-sorbitol (1,1-GPS),1-O-α-D-glucopyranosyl-D-mannitol (1,1-GPM), maltitol syrup, sorbitolsyrup, fructo-oligosaccharides or mixtures of them, as well as mixturesof sugars and sugar alcohols.

In a further preferred embodiment of the invention the chewing gumaccording to the invention is a sugar-free chewing gum. In connectionwith the present invention, a “sugar-free chewing gum” is understood tobe a chewing gum in which neither the chewing gum itself nor the coatinglayer contain as sweeteners any of the sugars named above; that is,neither sucrose, invert liquid sugar, invert sugar syrup, dextrose,glucose syrup, trehalose, trehalulose, tagatose, lactose, maltose,fructose, leucrose, isomaltulose (palatinose), condensed palatinose andhydrated condensed palatinose, or mixtures of them, but instead sugarsubstitutes. In the preferred embodiment of the invention the sugar-freechewing gum according to the invention is a chewing gum having a maximumcontent of 0.5% by weight, based on the dry weight, of the sugarsmentioned above.

The term “sugar substitute” includes all the substances other than thesugars named above that can be used to sweeten foods. The term “sugarsubstitute” includes, in particular, substances such as hydratedmonosaccharide and disaccharide sugar alcohols, such as lactitol,xylitol, sorbitol, mannitol, maltitol, erythritol, isomaltitol, 1,6-GPS,1,1-GPS, 1,1-GPM, sorbitol syrup, maltitol syrup, andfructo-oligosaccharides. Thus the sugar-free chewing gums according tothe invention are preferably characterized by the fact that neither thechewing gum itself or the coating layer contains as a sweetener lactose,maltose, fructose, leucrose, palatinose, condensed palatinose, hydratedcondensed palatinose, fructo-oligosaccharides, lactitol, sorbitol,xylitol, mannitol, maltitol, erythritol, 1,6-GPS, 1,1-GPS, 1,1-GPM,sorbitol syrup, maltitol syrup, or mixtures of them. Sugar alcohols suchas sorbitol or sorbitol syrup, mannitol, xylitol, lactitol, maltitol ormaltitol syrup, 1,1-GPS, 1,6-GPS, 1,1-GPM or mixtures of them arepreferred according to the invention. Sugar alcohols have the advantagethat they contain fewer calories per 100 g and that they are notdegraded to acids by bacteria of the oral flora, or are degraded onlyvery slowly, so that they have no cariogenic action.

A preferably used mixture of 1,6-GPS and 1,1-GPM is isomalt, in whichthe 1,6-GPS and 1,1-GPM are present in equimolar or nearly equimolaramounts. 1,6-GPS-enriched mixtures of 1,6-GPS and 1,1-GPM containing 57%by weight to 99% by weight 1,6-GPS and 43% by weight to 1% by weight1,1-GPM, 1,1-GPM-enriched mixtures of 1,6-GPS and 1,1-GPM having 1% byweight to 43% by weight 1,6-GPS and 57% by weight to 99% by weight1,1-GPM, and mixtures of 1,6-GPS, 1,1-GPS and 1,1-GPM can be used assweeteners in the chewing gums, especially sugar-free chewing gums,according to the invention, both in the chewing gum itself and in theenveloping layer. Mixtures of 1,6-GPS and 1,1-GPM enriched with 1,6-GPSand enriched with 1,1-GPM are disclosed in German Patent 195 32 396 C2,and the content of the disclosure in that patent dealing with thedescription and production of the sweetening mixtures enriched with1,6-GPS and with 1,1-GPM are completely included in the content of thedisclosure of the present teaching. Mixtures of 1,6-GPS and 1,1-GPM aredisclosed, for example, in EP 0 625 578 B1, and the content of thedisclosure of that patent dealing with the description and production ofsweetening mixtures containing 1,1-GPS, 1,6-GPS and 1,1-GPM arecompletely included in the content of the disclosure of the presentteaching.

Another mixture preferred according to the invention which can be usedin the chewing gums according to the invention, especially sugar-freechewing gums, is a syrup with a dry content of 60 to 80%, consisting ofa mixture of hydrated starch hydrolyzate syrup and isomalt powder orisomalt syrup, in which the dry content of the syrup comprises 7 to 52%(w/w) 1,6-GPS, 24.5 to 52% (w/w) 1,1-GPM, 0 to 52% (w/w) 1,1-GPS, 0 to1.3% (w/w) sorbitol, 2.8-13.8% (w/w) maltitol, 1.5 to 4.2% (w/w)maltotriitol and 3.0 to 13.5% (w/w) higher polyols. Such a syrup isdisclosed in EP 1 194 042 B1, and the content of the disclosure of thatpatent with respect to the description and production of syrupscomprising hydrated starch hydrolysis syrup and isomalt power or isomaltsyrup is completely included in the content of the disclosure of thepresent teaching.

The sugar-free chewing gum according to the invention, which isenveloped with at least one layer comprising the composite materialaccording to the invention can, for instance, be a hard-coatedsugar-free chewing gum containing essentially hygroscopic sugar-freesweetener, in which the chewing gum core has a water content of lessthan 2.5% by weight, based on the weight of the core. The essentiallyhygroscopic sweetener can, for instance, be sorbitol or hydratedisomaltulose. Such sugar-free hard-coated chewing gums are described inWO 88/08671, and the content of the disclosure of that patent withrespect to the description and production of the hard-coated sugar-freechewing gums is completely included in the content of the disclosure ofthe present teaching.[

Another embodiment of the invention provides that both the sugar-freechewing gum according to the invention and the sugar-free chewing gumaccording to the invention in the chewing gum itself and/or in theenveloping layer can contain, aside from the sugars and/or sugarsubstitutes named above, one or more intensive sweeteners. Intensivesweeteners are compounds distinguished by an intense sweet taste withlittle or negligible nutritional value. It is particularly providedaccording to the invention that the intensive sweetener used in thechewing gum according to the invention is cyclamate, such as sodiumcyclamate, saccharin, such as saccharin sodium, Aspartame®,glycyrrhizin, neohesperidine-dihydrochalcone, thaumatin, monellin,acesulfam, stevioside, altiam, sucralose, or a mixture of those. Byusing such intensive sweeteners, the proportion of sugars in particularcan be reduced and nevertheless the predominantly sweet taste can bemaintained.

A further embodiment of the invention; provides that the chewing gumaccording to the invention has not just one enveloping layer,particularly a sugar-coated layer comprising a sparingly water-solublecalcium salt or composite materials comprising them, but at least up tosome hundred such enveloping layers, particularly sugar-coated layers.It is possible according to the invention for the individual layers tocontain the same sweetener or the same sweetener. Obviously, it is alsopossible according to the invention that the individual layers can alsocomprise different sweeteners. Such sugar-coated chewing gum productsare therefore enveloped by layer sequences having different sweetenercompositions. By a suitable selection of the sequence and number of thecoating steps with the different sweeteners, it is possible to produceintentionally chewing gums with desired properties.

For instance, the chewing gum according to the invention can first beenveloped with 1 to some 45 sugar-coated layers containing the mixtureof 1,6-GPS and 1,1-GPM enriched with 1,1-GPM. Then 1 to 45 layers of themixture of 1,6-GPS and 1,1-GPM enriched with 1,6-GPS are coated on thoselayers. Such a sugar-coated chewing gum is distinguished by an over-allhigher sweetness in comparison with the chewing gums coated withhydrated isomaltulose, for example, because of the higher solubility andgreeter sweetening power of the 1,6-GPS-enriched mixture making up theouter coating. Such a sequence of layers is described in German Patent195 32 396 C2, and the content of the disclosure of that patent withrespect to the description and production of chewing gum with that layersequence is completely included in the content of the disclosure of thepresent teaching.

The chewing gum according to the invention can, for instance, be ahard-coated chewing gum having the sugar coating comprising multiplelayers comprising about 50% to about 100% xylitol and multiple layerscomprising about 50% to about 100% isomaltulose. Such chewing gums aredisclosed in WO 93/18663, and the content of the disclosure of thatpatent with respect to the description and production of chewing gumswith this layer sequence is completely included in the content of thedisclosure of the present teaching.

A further embodiment provides that the individual sugar-coated layersenveloping the chewing gum comprise the same calcium salt and/or thesame composite of it. Obviously, it is also possible according to theinvention for the individual layers enveloping the chewing gum tocomprise different calcium salts and/or different composites thereof. Itis also obviously possible for individual layers to contain no calciumsalt or no composite of it.

The layer enveloping the chewing gum which comprises the sparinglysoluble calcium salt results advantageously in the release of thecalcium salt occurring more simply than when the salt is directlyincorporated into the chewing gum mass, in which the incorporatedcalcium salt remains strongly adherent to the sticky matrix of thechewing mass. The layer enveloping the chewing gum dissolves veryrapidly on chewing in the mouth. Thus it makes the required amount ofactive substance available in the mouth, which advantageously assureseffective mineralization of the teeth. The addition of the calcium saltand/or composites thereof does not affect the ‘crunch’, i.e., thecrunchiness of the chewing gum.

According to a particular embodiment the layer enveloping the chewinggum according to the invention comprises sugars and/or sugar alcohols.The monosaccharide, disaccharide and oligosaccharide sugar typespreferred for use in that layer, such as dextrose, fructose and sucrose,glucose syrup, liquid sugar and related products, dried glucose syrupand other starch saccharification products can also be sugarsubstitutes, especially sugar alcohols.

It is advantageous for the layer comprising the sugars and/or sugaralcohols to dissolve rapidly in the mouth. They can also be appliedparticularly well to a chewing gum core aside from the sweet tasteexperience.

Although some of the ingredients (sugars) damage teeth, consumption ofthe chewing gum according to the invention results not only in thepleasurable experience but also to care and preservation of the teeth,as well as to mineralization of the enamel and/or of the dentine.Therefore it is possible to omit without harm the tooth care (usuallywith toothbrushes, toothpastes and/or mouthwash) that has previouslybeen needed but is not always possible after eating.

Sorbitol or sorbitol syrup, mannitol, xylitol, lactitol, isomalt,maltitol or maltitol syrup are preferred sugar alcohols according to theinvention. These substances have the advantage that they contain fewercalories per hundred grams and furthermore the degradation of the sugaralcohols to acids by some bacteria of the oral cavity occurs so slowlythat they have no cariogenic action. The addition, according to theinvention, of composites according to the invention to chewing gumscomprising sugar substitutes results in mineralization of the teethduring and/or after the enjoyment of the chewing gum, thus contributingto retention of healthy teeth. Because of their physico-chemicalproperties, the sugar alcohols are particularly suitable for productionof thin layers, especially in the pan-coating process. It isparticularly preferable to use isomalt in the enveloping layer becausethis sugar alcohol has a relatively high glass transition temperature,which makes the processing especially easier.

The layer enveloping the chewing gum can be produced in differentmanners, e.g., by multiple immersion of the chewing gum core in anappropriate solution and/or dispersion.

According to a preferred embodiment of the invention at least one of thelayers enveloping the chewing gum is a pan-coated layer. That is, thelayer is applied to the chewing gum in the pan-coating process. Thepan-coated layer (cover) comprises a smooth or wrinkled [coating] havingsugars and/or sugar alcohols, chocolate or other glazings applied arounda liquid, soft or solid core by means of the pan-coating process (asdescribed above).

According to another embodiment the chewing gum is a filled chewing gum.

Chewing gums that comprise composite materials according to theinvention incorporated into the chewing mass release only trace amountsof the active substance because of their sticky consistency. Biting intothe filled chewing gum releases the composite material according to theinvention that is contained in the filling directly into the mouth, andso can act better than in the usual chewing gums.

The filled chewing gum can furthermore have at least one layercomprising the composite materials according to the invention envelopingthe chewing gum.

According to a further preferred embodiment of the present invention thesweetener comprises a dissolving component. This component or matrixdissolves in the mouth through contact with the saliva. The dissolutioncan also be accomplished by longer residence time in the mouth(especially more than five minutes) and/or dissolves in the mouththrough contact with the saliva. The dissolution can also beaccomplished by longer residence time in the mouth (especially more thanfive minutes) and/or by sucking. The component or matrix here isunderstood, for instance, to be the sugar matrix or basic mass of abonbon, a gummy bonbon or also a filling.

It is particularly preferred that the dissolving component or matrix bein the calcium salts and/or composite materials comprising themcontained in the candy. That results advantageously in the dissolvingcomponent being able to release the active substance in it into themouth. That is particularly important for those candies with which theactive substance is not otherwise released in large amounts.

That can be advantageous, for instance, for a filled chewing gum. Thecalcium salts and/or composite materials comprising them according tothe invention are incorporated into a solid, gel-like or liquid fillingthat leaves the chewing gum when the gum is bitten in the mouth andreleases the active substance. If the filling is liquid, it mixes withthe saliva. It is also possible for the calcium salts and/or thecomposite materials comprising them to be processed, for example, intogranulated sugar beads in a chewing gum. It is likewise possible for thematerials according to the invention to be applied to the candy as afine dust, for instance, together with release agents for chewing gums(e.g., talcum) or acidic drops (which are often dusted with powderedsugar, for example, to protect against sticking together).

The active substance in the dissolving component or matrix does notremain adherent in or to a component that does not dissolve, as in thecase of incorporation into the chewing mass of a chewing gum. Thus therequired amount of active substance that advantageously assureseffective mineralization of the teeth is made available in the mouth.

According to a particularly preferred embodiment of the invention, thecandy comprises essentially at least one dissolving component or matrix.It is particularly advantageous in this case, according to theinvention, that there are no components of the candy that allow theactive substance to be bound in the mouth after sucking or dissolvingand so not available for mineralization of the tooth material.Appropriate candies can, for instance, be filled or unfilled caramels,gummy bonbons, jellies, foamed sugar products, licorice products, coatedtablets or pastilles.

According to a further preferred embodiment the candy contains fragrancesubstances, sweeteners, fillers and/or other additives (such as glycerolor mineral salts, e.g., Zn²⁺ or Mg²⁺).

Essentially any natural fragrance material or one identical with naturalfragrance material, such as fruit fragrances, can be used. They can becontained especially in solid or liquid fruit preparations, fruitextracts or fruit powders. Pineapple, apple, apricot, banana,blackberry, strawberry, grapefruit, blueberry, raspberry, passion fruit,orange, sour cherry, red and black currant, woodruff and lemon arepreferred.

Other fragrances, especially aromatic soils such as peppermint oil,curly mint oil, eucalyptus oil, anise oil, fennel oil, caraway oil andsynthetic aromatic oils can also be used. That is done particularlypreferably in herbal bonbons and cough lozenges as well as in chewinggums.

Other flavoring additives can be, for example: milk, yogurt, cream,butter, honey, malt, caramel, licorice, wine, almond, pistachio,hazelnut or walnut kernels and other high-protein oil seeds and peanuts,coconut, cacao, chocolate, cola or vanilla.

The candy according to the invention can also contain active substancessuch as menthol and/or vitamins. Organophosphates such as1-hydroxyethane-1,1-diphosphonic acid,phosphonopropane-1,2,3-tricarboxylic acid (sodium salt) or1-azacycloheptane-2,2-diphosphonic acid (sodium salt) and/orpyrophosphates, which reduce formation of dental calculus, can also beadded.

Sweeteners such as saccharin sodium, acesulfam-K, Aspartame®, sodiumcyclamate, stevioside, thaumatin, sucrose, lactose, maltose, fructose orglycyrrhizin are also preferably contained. With those, the proportionof sugar can be reduced and the predominantly sweet taste can still beretained.

All the preservatives allowed for foods can be used as preservatives,such as sorbic or benzoic acids and their derivatives, such as sodiumbenzoate and para-hydroxybenzoate (sodium salt), sulfur dioxide orsulfurous acid, or sodium or potassium nitrite. Dyes and pigments canalso be contained to achieve a pleasing appearance.

A further object of the present invention is use of at least onecomposite material according to the invention in candies, especiallyconfectioneries, as ingredients with a positive effect on dental health.

In particular, the calcium salts and/or the composite materialscomprising them, or the candy containing them, are used for dental careand preservation and also for mineralization of the enamel and/or thedentine. Use of the materials according to the invention can thuscounteract dental caries. Aside from the pleasant taste, the candyaccording to the invention can also be used to prevent caries.

According to a further preferred embodiment, the compositions accordingto the invention comprise not only the calcium salts and/or thecomposite materials comprising them according to the invention but alsoat least one fluoride salt. It has been found, surprisingly, thataddition of fluoride results in a synergistic increase of the nucleatingeffect of the composite materials according to the invention. It isparticularly preferable to add sodium and/or potassium fluoride. Whenthe active substances and small amounts of fluoride are addedsimultaneously, there is a synergistic effect of about five-fold.

According to the invention, proportions of 0.01 to 1.2% by weight,especially 0.1 to 0.90% by weight fluoride salt are preferred, dependingon the fluoride salt used (e.g., sodium fluoride). This corresponds to aproportion of 0.05 to 0.15% by weight fluoride ions, and particularly,0.08 to 0.12% by weight.

According to the invention, proportions of 0.05 to 0.15% by weight,especially 0.08 to 0.12% by weight fluoride are preferred, based on theamount of fluoride ions.

A further object of the present invention is compositions to induce orpromote new formation of bone tissue containing calcium salts and/or thecomposite materials comprising them according to the invention.

It has been found that that test subjects perceive a particularly good,smooth, and clean feeling in the mouth during and after use of thecompositions according to the invention, especially in the form oftoothpastes.

The following examples are intended to explain the object of theinvention in greater detail.

EXAMPLES 1. Production of Composite Materials by Precipitation Reactionsin the Presence of the Protein Components 1.1 Production of anApatite-Protein Composite

To produce the apatite-gelatin composite, 2,000 ml of deionized watercontaining 44.10 g (0.30 mole) CaCl₂.2H₂O (Fisher Chemicals, reagentgrade) is placed in a 4-liter beaker thermostatted at 25° C. Separately,35 g of gelatin (Type AB, DGF-Stoess, Eberbach) is dissolved in 350 mldeionized water at about 50° C. The two solutions are combined andstirred vigorously with a propeller stirrer. The pH is adjusted to 7.0with dilute aqueous base.

300 mL of a 0.6 M solution of (NH₄)₂HPO₄ solution, previously adjustedto pH 7.0, is added evenly to this solution of gelatin and calcium salt,with vigorous stirring, over a period of 120 minutes, while the pH isheld constant at 7.0 by controlled addition of dilute aqueous base.After the addition is complete, the stirring is continued for a further24 hours.

Then the dispersion is filled into centrifuge cups and the solids areseparated from the solution by centrifuging.

The dry composite material contains 43% by weight of organic, i.e.,proteinaceous, material. This proportion is determined by ashing thematerials for 3 hours at 800° C. or by expert evaluation of athermogravimetric measurement or by a combustion carbon analysis (CHN)or by a Kjeldahl nitrogen analysis. In each case, the amount of ammoniumchloride contaminant must be subtracted.

2. Production of Composite Materials by Incorporating Dispersions ofSurface-Modified Calcium Salts into Protein Components 2.1 CompositeMaterial of Hydroxyapatite and AB Gelatin

Solutions A and B are First Prepared Separately.

Solution A.

25.4 g calcium nitrate tetrahydrate and 8.50 g diammonium hydrogenphosphate are each dissolved in 100 g deionized water. The two solutionsare mixed, with formation of a white precipitate. After addition of 10ml 37% by weight HCl, one gets a clear solution.

Solution B.

200 ml deionized water, 200 ml of a 25% by weight aqueous ammoniasolution and 20 g Plantacare® were combined and cooled to 0° C. in anice bath. Solution A was added to Solution B with vigorous stirring,with formation of a precipitate of hydroxyapatite. After removal ofexcess ammonia, the dispersion was purified by dialysis. The dispersionis evaporated in a rotary evaporator, with measurement of the amount ofwater removed, until the proportion of solids in the dispersion,calculated as hydroxyapatite, was 7.5% by weight.

This dispersion was added, at room temperature, to 100 ml of a 10% byweight aqueous solution of AB gelatin (manufacturer: DGF Stoess) made asin Example 1.1. Then the mixture was heated to 80° C. and stirred for 5minutes at that temperature. Then the product was allowed to solidify atroom temperature, producing the composite material.

3. Dental Creams with Calcium Salt Composite Materials

Example formulation 4.1 4.2 4.3 4.4 4.4 Sident ® 8 10.0% by  10.0% by 10.0% by  10.0% by  10.0% by  weight weight weight weight weightSident ® 22S 7.0% by 7.0% by 7.0% by 7.0% by 7.0% by weight weightweight weight weight Sipernat ® 0.8% by 0.8% by 0.8% by 0.8% by 0.8% by320DS weight weight weight weight weight Glycerin 1.0% by 0.1% by 1.0%by 0.1% by 0.05% by  solution weight weight weight weight weightcontaining 10% by weight composite material Polywax ® 1550 2.0% by 2.0%by 2.0% by 2.0% by 2.0% by weight weight weight weight weight Texapon ®K 1.5% by 1.5% by 1.5% by 1.5% by 1.5% by 1296 weight weight weightweight weight Titanium 1.0% by 1.0% by 1.0% by 1.0% by 1.0% by dioxideweight weight weight weight weight Cekol ® 500 1.0% by 1.0% by 1.0% by1.0% by 1.0% by T weight weight weight weight weight Sodium 0.33% by 0.33% by  0.33% by  0.33% by  0.33% by  fluoride weight weight weightweight weight Sodium 0.25% by  0.25% by  0.25% by  0.25% by  0.25% by benzoate weight weight weight weight weight Fragrance 1.0% by 1.0% by1.0% by 1.0% by 1.0% by weight weight weight weight weight Tagat ® S0.2% by — — 0.2% by 0.2% by weight weight weight Saccharin 0.15% by 0.15% by  0.15% by  0.15% by  0.15% by  sodium weight weight weightweight weight Trisodium 0.10% by  0.10% by  0.10% by  0.10% by  0.10%by  phosphate weight weight weight weight weight Sorbitol (70% 31.0% by 31.0% by  31.0% by  31.0% by  31.0% by  in water) weight weight weightweight weight Water to make 100% to make 100% to make 100% To make 100to make 100% by weight by weight by weight % by weight by weight

The following commercial products were used:

Plantacare® 1200: C₁₂-C₁₈-alkyl glycoside

-   -   ca. 50% by weight in water    -   Manufacturer: Cognis        Sident® 8: Synthetic amorphous silicic acid, BET 60 m²/g    -   Compacted bulk density: 350 g/L    -   Manufacturer: DEGUSSA        Sident® 22 S: Silicic acid hydrogel, BET 140 m²/g    -   Compacted bulk density: 100 g/L    -   Manufacturer: DEGUSSA        Polywax® 1550: Polyethylene glycol, MW: 1550    -   Softening point 45-50° C.    -   Manufacturer: RWE/DEA        Texapon® K 1296: Sodium lauryl sulfate powder    -   Manufacturer: Cognis        Cekol® 500 T: Sodium carboxymethyl cellulose    -   Viscosity (2% in water, Brookfield LVF, 20° C.):    -   350-700 mPa·s    -   Supplier: Noviant        Tagat® S: Polyoxyethylene-(20)-glyceryl monostearate    -   Manufacturer: Tego Cosmetics (Goldschmidt)

1. A composition comprising sparingly water-soluble calcium salts in theform of individual crystallites or particles having a mean particlediameter of less than 1,000 nm wherein the individual crystallites orparticles are platelet-like.
 2. The composition of claim 1 wherein thelength of the platelet-like crystallites or particles is from 10 to 150nm and the width is from 5 to 150 nm.
 3. The composition of claim 1wherein the length to width radio of the crystallites or particles isfrom 1 to
 4. 4. The composition of claim 1 wherein the area of thecrystallites or particles is from 0.1×10⁻¹⁵ m² to 90×10⁻¹⁵ m².
 5. Thecomposition of claim 4 wherein the area is from 1.5×10⁻¹⁵ m² to 15×10⁻¹⁵m².
 6. The composition of claim 1 further comprising a polymercomponent.
 7. The composition of claim 6 wherein the polymer componentis selected from the group consisting of proteins, protein hydrolysatesand derivatives of protein hydrolysates, polyacrylic acids andpolymethacrylic acids.
 8. The composition of claim 7 wherein the polymercomponent is a protein hydrolysate.
 9. The composition of claim 8wherein the protein hydrolysate is selected from the group consisting ofpolyaspartic acids, alginic acids, pectins, deoxyribonucleic acids andribonucleic acids.
 10. The composition of claim 7 wherein the polymercomponent is a protein.
 11. The composition of claim 10 wherein theproportion of the protein component of the composition is from 0.1 to80% by weight.
 12. The composition of claim 11 wherein the proportion isfrom 30 to 50% by weight.
 13. The composition of claim 1 wherein thesparingly water-soluble calcium salts are made by the process comprisingcontacting an aqueous solution of a water-soluble calcium salt and anaqueous solution of a water-soluble phosphate and/or fluoride salt at apH of from 5 and pH 9 to form a precipitate comprising the sparinglywater-soluble calcium salts.
 14. A method comprising contacting a toothwith an effective amount of a composition of claim 1 whereby the dentalenamel of the tooth is hardened or biomineralization is induced orpromoted.
 15. A method comprising contacting a tooth with an effectiveamount of a composition of claim 1 whereby the tooth is protected fromthe physiological, chemical, physical and/or microbiological damagecaused by bacterial activity.
 16. An oral and dental care compositioncomprising a composition of claim
 1. 17. A method for promoting theformation of new bone tissue comprising contacting bone with aneffective amount of a composition of claim 1.